{{infobox disease |name	Melanoma |Image Melanoma.jpg |Caption |Width 225 |DiseasesDB 7947 |ICD10 |ICD9 |ICDO |OMIM 155600 |MedlinePlus 000850 |eMedicineSubj derm |eMedicineTopic 257 |eMedicine_mult |MeshID D008545 |BioVex }}

Melanoma () is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye (see uveal melanoma). Melanoma can occur in any part of the body that contains melanocytes.

Melanoma is less common than other skin cancers. However, it is much more dangerous and causes the majority (75%) of deaths related to skin cancer. Worldwide, doctors diagnose about 160,000 new cases of melanoma yearly. The diagnosis is more frequent in women than in men and is particularly common among Caucasians living in sunny climates, with high rates of incidence in Australia, New Zealand, North America, and northern Europe. According to a WHO report about 48,000 melanoma related deaths occur worldwide per year.

The treatment includes surgical removal of the tumor, adjuvant treatment, chemo- and immunotherapy, or radiation therapy. The chance of a cure is greatest when the tumor is discovered while it is still small and thin, and can be entirely removed surgically.

Signs and symptoms

Early signs of melanoma are changes to the shape or color of existing moles or in the case of nodular melanoma the appearance of a new lump anywhere on the skin (such lesions should be referred without delay to a dermatologist). At later stages, the mole may itch, ulcerate or bleed. Early signs of melanoma are summarized by the mnemonic "ABCDE":

Asymmetry

Borders (irregular)

Color (variegated), and

Diameter (greater than , about the size of a pencil eraser)

Evolving over time

These classifications do not however apply to the most dangerous form of melanoma nodular melanoma which has its own classifications:

Elevated above the skin surface

Firm to the touch

Growing.

Metastatic melanoma may cause non-specific paraneoplastic symptoms including loss of appetite, nausea, vomiting and fatigue. Metastasis of early melanoma is possible, but relatively rare: less than a fifth of melanomas diagnosed early become metastatic. Brain metastases are particularly common in patients with metastatic melanoma.

Cause

All cancers are caused by damage to the DNA inside cells. This damage can be inherited in the form of genetic mutations, but in most cases it builds up over a person's lifetime and is caused by factors in their environment. DNA damage causes the cell to grow out of control, leading to a tumor. Melanoma is usually caused by damage from UV light from the sun, but UV light from sunbeds can also contribute to the disease.

Natural history

The earliest stage of melanoma starts when the melanocytes begin to grow out of control. Melanocytes are found between the outer layer of the skin (the epidermis) and the next layer (the dermis). This early stage of the disease is called the radial growth phase, and the tumour is less than 1mm thick. Because the cancer cells have not yet reached the blood vessels lower down in the skin it is very unlikely that this early-stage cancer will spread to other parts of the body. If the melanoma is detected at this stage then it can usually be completely removed with surgery.

When the tumour cells start to move in a different direction — vertically up into the epidermis and into the papillary dermis — the behaviour of the cells changes dramatically.

The next step in the evolution is the invasive radial growth phase, which is a confusing term, however it explains the next step in the process of the radial growth, when individual cells start to acquire invasive potential. This step is important – from this point on the melanoma is capable of spreading. The Breslow's depth of the lesion is usually less than, the Clark level is usually 2.

The following step in the process is the invasive melanoma — the vertical growth phase (VGP). The tumour attains invasive potential, meaning it can grow into the surrounding tissue and can spread around the body through blood or lymph vessels. The tumour thickness is usually more than , and the tumour involves the deeper parts of the dermis.

The host elicits an immunological reaction against the tumour (during the VGP), which is judged by the presence and activity of the TILs (tumour infiltrating lymphocytes). These cells sometimes completely destroy the primary tumour, this is called regression, which is the latest stage of the melanoma development. In certain cases the primary tumour is completely destroyed and only the metastatic tumour is discovered.

Genetics

In some cases, melanoma runs in families. Several different genes have been identified as increasing the risk of developing melanoma. Some rare genes have a relatively high risk of causing melanoma; some more common genes, such as a gene called MC1R that causes red hair, have a relatively low risk. Genetic testing can be used to determine whether a person has one of the currently known mutations.

A number of rare mutations, which often run in families, are known to greatly increase one’s susceptibility to melanoma. One class of mutations affects the gene CDKN2A. An alternative reading frame mutation in this gene leads to the destabilization of p53, a transcription factor involved in apoptosis and in fifty percent of human cancers. Another mutation in the same gene results in a non-functional inhibitor of CDK4, a [cyclin-dependent kinase] that promotes cell division. Mutations that cause the skin condition Xeroderma Pigmentosum (XP) also seriously predispose one to melanoma. Scattered throughout the genome, these mutations reduce a cell’s ability to repair DNA. Both CDKN2A and XP mutations are ''highly penetrant''.

Familial melanoma is genetically heterogeneous, and loci for familial melanoma have been identified on the chromosome arms 1p, 9p and 12q. Multiple genetic events have been related to the pathogenesis (disease development) of melanoma. The multiple tumor suppressor 1 (CDKN2A/MTS1) gene encodes p16INK4a — a low-molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) — which has been localised to the p21 region of human chromosome 9.

Other mutations confer lower risk but are more prevalent in the population. People with mutations in the MC1R gene, for example, are two to four times more likely to develop melanoma than those with two wild-type (typical unaffected type) copies of the gene. MC1R mutations are very common; in fact, all people with red hair have a mutated copy of the gene.

Two-gene models of melanoma risk have already been created, and in the future, researchers hope to create genome-scale models that will allow them to predict a patient’s risk of developing melanoma based on his or her genotype.

In addition to identifying high-risk patients, researchers want to identify high-risk lesions (abnormal area of tissue) within a given patient. Many new technologies, such as optical coherence tomography(OCT), are being developed to accomplish this. OCT allows pathologists to view 3-D reconstructions of the skin and offers more resolution than past techniques could provide. In vivoconfocal microscopy and fluorescently tagged antibodies are also proving to be valuable diagnostic tools.

Mutation of the MDM2 SNP309 gene is associated with increased risk of melanoma in younger women.

UV radiation from tanning beds

In July 2009, the IARC released a report that categorized tanning beds as “carcinogenic to humans”. The agency, which is part of the World Health Organization (WHO), previously classified tanning beds as “probably carcinogenic”. The change comes after an analysis of more than 20 epidemiological studies indicating that people who begin using tanning devices before age 30 are 75% more likely to develop melanoma.

In December 2009, Julie Morgan, Labour MP for Cardiff North, introduced a Private Member's Bill before Parliament aimed at preventing under-18s using sunbeds. MPs considered the evidence, including research from a UK cancer charity . The research found that a quarter of a million children in England between the ages of 11 and 17 regularly used sunbeds. The bill was passed in April 2011 and the Sunbed (Regulation) Bill restricts the use of sunbeds to over-18s in England and Wales (Scotland already had this legislation). All sunbed salons will have to be staffed and provide accurate health information on the dangers of sunbeds.

Diagnosis

There is no blood test for detecting melanomas. Visual diagnosis of melanomas is still the most common method employed by health professionals. To detect melanomas (and increase survival rates), it is recommended to learn what they look like (see "ABCD" mnemonic below), to be aware of moles and check for changes (shape, size, color, itching or bleeding) and to show any suspicious moles to a doctor with an interest and skills in skin malignancy.

A popular method for remembering the signs and symptoms of melanoma is the mnemonic "ABCDE":

''A''symmetrical skin lesion.

''B''order of the lesion is irregular.

''C''olor: melanomas usually have multiple colors.

''D''iameter: moles greater than 6 mm are more likely to be melanomas than smaller moles.

''E''nlarging: Enlarging or evolving

A weakness in this system is the D. Many melanomas present themselves as lesions smaller than 6 mm in diameter; and all melanomas were malignant on day 1 of growth, which is merely a dot. An astute physician will examine all abnormal moles, including ones less than 6 mm in diameter. Seborrheic keratosis may meet some or all of the ABCD criteria, and can lead to false alarms among laypeople and sometimes even physicians. An experienced doctor can generally distinguish seborrheic keratosis from melanoma upon examination, or with dermatoscopy.

Some will advocate the system "ABCDE", with E for evolution. Certainly moles which change and evolve will be a concern. Alternatively, some will refer to E as elevation. Elevation can help identify a melanoma, but lack of elevation does not mean that the lesion is not a melanoma. Most melanomas are detected in the very early stage, or in-situ stage, before they become elevated. By the time elevation is visible, they may have progressed to the more dangerous invasive stage.

However, Nodular melanomas do not fulfill these criteria, having their own mnemonic "EFG":

''E''levated: the lesion is raised above the surrounding skin.

''F''irm: the nodule is solid to the touch.

''G''rowing: the nodule is increasing in size.

A recent and novel method of melanoma detection is the "Ugly Duckling Sign" It is simple, easy to teach, and highly effective in detecting melanoma. Simply, correlation of common characteristics of a person's skin lesion is made. Lesions which greatly deviate from the common characteristics are labeled as an "Ugly Duckling", and further professional exam is required. The "Little Red Riding Hood" sign suggests that individuals with fair skin and light colored hair might have difficult-to-diagnose amelanotic melanomas. Extra care and caution should be rendered when examining such individuals as they might have multiple melanomas and severely dysplastic nevi. A dermatoscope must be used to detect "ugly ducklings", as many melanomas in these individuals resemble non-melanomas or are considered to be "wolves in sheep clothing". These fair skinned individuals often have lightly pigmented or amelanotic melanomas which will not present easy-to-observe color changes and variation in colors. The borders of these amelanotic melanomas are often indistinct, making visual identification without a dermatoscope (dermatoscopy) very difficult.

People with a personal or family history of skin cancer or of dysplastic nevus syndrome (multiple atypical moles) should see a dermatologist at least once a year to be sure they are not developing melanoma.

Moles that are irregular in color or shape are often treated as candidates of melanoma. Following a visual examination and a dermatoscopic exam, or an ''in vivo'' diagnostic tools such as a confocal microscope, the doctor may biopsy the suspicious mole. If the mole is malignant, the mole and an area around it need excision.

The diagnosis of melanoma requires experience, as early stages may look identical to harmless moles or not have any color at all. A skin biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis and in defining the severity of the melanoma. Amelanotic melanomas and melanomas arising in fair skinned individuals (see the "Little Red Riding Hood" sign) are very difficult to detect as they fail to show many of the characteristics in the ABCD rule, break the "Ugly Duckling" sign, and are very hard to distinguish from acne scarring, insect bites, dermatofibromas, or lentigines.

Total body photography, which involves photographic documentation of as much body surface as possible, is often used during follow-up of high-risk patients. The technique has been reported to enable early detection and provides a cost-effective approach (being possible with the use of any digital camera), but its efficacy has been questioned due to its inability to detect macroscopic changes. The diagnosis method should be used in conjunction with (and not as a replacement for) dermscopic imaging, with a combination of both methods appearing to give extremely high rates of detection.

Surgical Treatment

''Excisional skin biopsy'' is the management of choice. Here, the suspect lesion is totally removed with an adequate (but minimal, usually 1 or 2 mm) ellipse of surrounding skin and tissue. In order not to disrupt the local lymphatic drainage, the preferred surgical margin for the initial biopsy should be narrow (1 mm). The biopsy should include the epidermal, dermal, and subcutaneous layers of the skin. This enables the histopathologist to determine the thickness of the melanoma by microscopic examination. This is described by Breslow's thickness (measured in millimeters). However, for large lesions such as suspected lentigo maligna, or for lesions in surgically difficult areas (face, toes, fingers, eyelids), a small punch biopsy in representative areas will give adequate information and will not disrupt the final staging or depth determination. In no circumstances should the initial biopsy include the final surgical margin (0.5 cm, 1.0 cm, or 2 cm), as a misdiagnosis can result in excessive scarring and morbidity from the procedure. Large initial excision will disrupt the local lymphatic drainage and can affect further lymphangiogram directed lymphnode dissection. A small punch biopsy can be utilized at any time where for logistical and personal reasons a patient refuses more invasive excisional biopsy. Small punch biopsies are minimally invasive and heal quickly, usually without noticeable scarring.

Lactate dehydrogenase (LDH) tests are often used to screen for metastases, although many patients with metastases (even end-stage) have a normal LDH; extraordinarily high LDH often indicates metastatic spread of the disease to the liver. It is common for patients diagnosed with melanoma to have chest X-rays and an LDH test, and in some cases CT, MRI, PET and/or PET/CT scans. Although controversial, sentinel lymph node biopsies and examination of the lymph nodes are also performed in patients to assess spread to the lymph nodes. A diagnosis of melanoma is supported by the presence of the S-100 protein marker.

Sometimes the skin lesion may bleed, itch, or ulcerate, although this is a very late sign. A slow-healing lesion should be watched closely, as that may be a sign of melanoma. Be aware also that in circumstances that are still poorly understood, melanomas may "regress" or spontaneously become smaller or invisible — however, the malignancy is still present. Amelanotic (colorless or flesh-colored) melanomas do not have pigment and may not even be visible. Lentigo maligna, a superficial melanoma confined to the topmost layers of the skin (found primarily in older patients) is often described as a "stain" on the skin. Some patients with metastatic melanoma do not have an obvious detectable primary tumor.

Classification

Melanoma is divided into the following stereotypes:

Lentigo maligna

Lentigo maligna melanoma

Superficial spreading melanoma

Acral lentiginous melanoma

Mucosal melanoma

Nodular melanoma

Polypoid melanoma

Desmoplastic melanoma

Amelanotic melanoma

Soft-tissue melanoma

See also:

Melanoma with small nevus-like cells

Melanoma with features of a Spitz nevus

Uveal melanoma

Staging

''Further context on cancer staging is available at TNM.''

Also of importance are the "Clark level" and "Breslow's depth" which refer to the microscopic depth of tumor invasion.

Melanoma stages:

Stage 0: Melanoma in Situ (Clark Level I), 99.9% Survival

Stage I/II: Invasive Melanoma, 85–99% Survival

T1a: Less than 1.00 mm primary tumor thickness, w/o Ulceration and mitosis < 1/mm2

T1b: Less than 1.00 mm primary tumor thickness, w/Ulceration or mitoses ≥ 1/mm2

T2a: 1.00–2.00 mm primary tumor thickness, w/o Ulceration

Stage II: High Risk Melanoma, 40–85% Survival

T2b: 1.00–2.00 mm primary tumor thickness, w/ Ulceration

T3a: 2.00–4.00 mm primary tumor thickness, w/o Ulceration

T3b: 2.00–4.00 mm primary tumor thickness, w/ Ulceration

T4a: 4.00 mm or greater primary tumor thickness w/o Ulceration

T4b: 4.00 mm or greater primary tumor thickness w/ Ulceration

Stage III: Regional Metastasis, 25–60% Survival

N1: Single Positive Lymph Node

N2: 2–3 Positive Lymph Nodes OR Regional Skin/In-Transit Metastasis

N3: 4 Positive Lymph Nodes OR Lymph Node and Regional Skin/In Transit Metastases

Stage IV: Distant Metastasis, 9–15% Survival

M1a: Distant Skin Metastasis, Normal LDH

M1b: Lung Metastasis, Normal LDH

M1c: Other Distant Metastasis OR Any Distant Metastasis with Elevated LDH

''Based Upon AJCC 5-Year Survival With Proper Treatment''

Prevention

Minimizing exposure to sources of ultraviolet radiation (the sun and sunbeds), following sun protection measures and wearing sun protective clothing (long-sleeved shirts, long trousers, and broad-brimmed hats) can offer protection. In the past it was recommended to use sunscreens with an SPF rating of 50 or higher on exposed areas as older sunscreens more effectively blocked UVA with higher SPF. Currently, newer sunscreen ingredients (avobenzone, zinc, and titanium) effectively block both UVA and UVB even at lower SPFs. However, there are questions about the ability of sunscreen to prevent melanoma. This controversy is well discussed in numerous review articles, and is rejected by most dermatologists. This correlation might be due to the confounding variable that individuals who used sunscreen to prevent burn might have a higher lifetime exposure to either UVA or UVB. See Sunscreen controversy for further references and discussions. Tanning, once believed to help prevent skin cancers, actually can lead to an increased incidence of melanomas. Even though tanning beds emit mostly UVA, which causes tanning, it by itself might be enough to induce melanomas.

A good rule of thumb for decreasing ultraviolet light exposure is to avoid the sun between the hours of 9 a.m. and 3 p.m. or avoid the sun when your shadow is shorter than your height. These are rough rules, however, and can vary depending on locality and individual skin cancer risk.

Almost all melanomas start with altering the color and appearance of normal-looking skin. This area may be a dark spot or an abnormal new mole. Other melanomas form from a mole or freckle that is already present in the skin. It can be difficult to distinguish between a melanoma and a normal mole. When looking for danger signs in pigmented lesions of the skin a few simple rules are often used. The “ABCDE” list, the "ugly duckling sign", and the "red riding hood" rule are defined and discussed under the heading "Detection" earlier in this article.

“Melanoma Monday” is the kick-off of May Melanoma Month with special activities nationally and locally. Also known as National Skin Self-Examination Day. People are encouraged to examine their skin for skin cancer. Since 1985, this program has helped to detect more than 188,000 suspicious lesions, including more than 21,500 suspected melanomas.

Treatment

Confirmation of the clinical diagnosis is either done with an excisional skin biopsy or a small full thickness sampling with a punch skin biopsy. This is usually followed with a follow up wider excision of the scar or tumor. Depending on the stage a sentinel lymph node biopsy is done as well, although controversy exists around trial evidence for this procedure. Treatment of advanced malignant melanoma is performed from a multidisciplinary approach.

Surgery

Elliptical excisional biopsies are performed to excise (followed by histological analysis and Breslow scoring, and in some cases may indeed actually remove) the tumor, but further surgery is often necessary to reduce the risk of recurrence. Punch biopsies are contraindicated in suspected melanomas, for fear of seeding tumour cells and hastening the spread of the malignant cells.

Complete surgical excision with adequate surgical margins and assessment for the presence of detectable metastatic disease along with short- and long-term followup is standard. Often this is done by a "wide local excision" (WLE) with 1 to 2 cm margins. Melanoma-in-situ and lentigo malignas are treated with narrower surgical margins, usually 0.2 to 0.5 cm. Many surgeons consider 0.5 cm the standard of care for standard excision of melanoma-in-situ, but 0.2 cm margin might be acceptable for margin controlled surgery (Mohs surgery, or the double bladed technique with margin control). The wide excision aims to reduce the rate of tumour recurrence at the site of the original lesion. This is a common pattern of treatment failure in melanoma. Considerable research has aimed to elucidate appropriate margins for excision with a general trend toward less aggressive treatment during the last decades.

Mohs surgery has been reported with cure rate as low as 77% and as high as 98% for melanoma-in-situ. CCPDMA and the "double scalpel" peripheral margin controlled surgery is equivalent to Mohs surgery in effectiveness on this "intra-epithelial" type of melanoma.

Melanomas which spread usually do so to the lymph nodes in the region of the tumor before spreading elsewhere. Attempts to improve survival by removing lymph nodes surgically (lymphadenectomy) were associated with many complications but unfortunately no overall survival benefit. Recently the technique of sentinel lymph node biopsy has been developed to reduce the complications of lymph node surgery while allowing assessment of the involvement of nodes with tumor.

Although controversial and without prolonging survival, "sentinel lymph node" biopsy is often performed, especially for T1b/T2+ tumors, mucosal tumors, ocular melanoma and tumors of the limbs. A process called lymphoscintigraphy is performed in which a radioactive tracer is injected at the tumor site in order to localize the "sentinel node(s)". Further precision is provided using a blue tracer dye and surgery is performed to biopsy the node(s). Routine H&E; staining, and immunoperoxidase staining will be adequate to rule out node involvement. PCR tests on nodes, usually performed to test for entry into clinical trials, now demonstrate that many patients with a negative SLN actually had a small number of positive cells in their nodes. Alternatively, a fine-needle aspiration may be performed and is often used to test masses.

If a lymph node is positive, depending on the extent of lymph node spread, a radical lymph node dissection will often be performed. If the disease is completely resected, the patient will be considered for adjuvant therapy.

Adjuvant treatment

High risk melanomas may require adjuvant treatment. In the United States most patients in otherwise good health will begin up to a year of high-dose interferon treatment, which has severe side effects but may improve the patient's prognosis. This claim is not supported by all research at this time, and in Europe interferon is usually not used outside the scope of clinical trials.

Metastatic melanomas can be detected by X-rays, CT scans, MRIs, PET and PET/CTs, ultrasound, LDH testing and photoacoustic detection.

Chemotherapy and immunotherapy

Various chemotherapy agents are used, including dacarbazine (also termed DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)) as well as local perfusion are used by different centers. They can occasionally show dramatic success, but the overall success in metastatic melanoma is quite limited. IL-2 (Proleukin) is the first new therapy approved for the treatment of metastatic melanoma in 20 years. Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in this disease, although only in a small percentage of patients. A number of new agents and novel approaches are under evaluation and show promise. Clinical trial participation should be considered the standard of care for metastatic melanoma.

Another molecule used in the immunotherapy is the lymphocyte cd4+. The lymphocyte cd4+ is isolated from the human body and produced in large amounts in laboratories. The cd4+ recognizes and kills the melanoma cells. It is used in melanoma metastasis and it gives good results in 2 months. Unfortunately this treatment is used only in some patients which their immune system recognizes the melanoma metastasis.

In 2005, a phase III clinical trial for a melanoma vaccine was halted after showing little benefit compared to placebo. On June 23, 2008, Israeli scientists from the Oncology Institute of the Hadassa Medical Center in Jerusalem announced they developed a vaccine that prevents recurrences of the disease among previous sufferers and increases chances of survival for current ones. One of the most promising current experimental treatment approaches, also an immunotherapy, is OncoVEX GM-CSF (BioVex Inc, Woburn, MA) which is currently in Phase 3 clinical trials following a very high level of efficacy having been observed in Phase 2.

Lentigo maligna treatment

Standard excision is still being done by most surgeons. Unfortunately, the recurrence rate is exceedingly high (up to 50%). This is due to the ill defined visible surgical margin, and the facial location of the lesions (often forcing the surgeon to use a narrow surgical margin). The narrow surgical margin used, combined with the limitation of the standard bread loafing technique of fixed tissue histology — result in a high "false negative" error rate, and frequent recurrences. Margin controlled (peripheral margins) is necessary to eliminate the false negative errors. If bread loafing is utilized, distances from sections should approach 0.1 mm to assure that the method approaches complete margin control.

Mohs surgery has been done with cure rate reported to be as low as 77%,

Some melanocytic nevi, and melanoma-in-situ (lentigo maligna) have resolved with an experimental treatment, imiquimod (Aldara) topical cream, an immune enhancing agent. Some dermasurgeons are combining the 2 methods: surgically excising the cancer and then treating the area with Aldara cream postoperatively for three months.

Radiation therapy

Radiation therapy is often used after surgical resection for patients with locally or regionally advanced melanoma or for patients with unresectable distant metastases. It may reduce the rate of local recurrence but does not prolong survival. Radioimmunotherapy of metastatic melanoma is currently under investigation. Radiotherapy has a role in the palliation of metastatic melanoma.

Prognosis

Features that affect prognosis are tumor thickness in millimeters (Breslow's depth), depth related to skin structures (Clark level), type of melanoma, presence of ulceration, presence of lymphatic/perineural invasion, presence of tumor-infiltrating lymphocytes (if present, prognosis is better), location of lesion, presence of satellite lesions, and presence of regional or distant metastasis. Certain types of melanoma have worse prognoses but this is explained by their thickness. Interestingly, less invasive melanomas even with lymph node metastases carry a better prognosis than deep melanomas without regional metastasis at time of staging. Local recurrences tend to behave similarly to a primary unless they are at the site of a wide local excision (as opposed to a staged excision or punch/shave excision) since these recurrences tend to indicate lymphatic invasion.

When melanomas have spread to the lymph nodes, one of the most important factors is the number of nodes with malignancy. Extent of malignancy within a node is also important; micrometastases in which malignancy is only microscopic have a more favorable prognosis than macrometastases. In some cases micrometastases may only be detected by special staining, and if malignancy is only detectable by a rarely employed test known as the polymerase chain reaction (PCR), the prognosis is better. Macrometastases in which malignancy is clinically apparent (in some cases cancer completely replaces a node) have a far worse prognosis, and if nodes are matted or if there is extracapsular extension, the prognosis is still worse.

When there is distant metastasis, the cancer is generally considered incurable. The five year survival rate is less than 10%. The median survival is 6 to 12 months. Treatment is palliative, focusing on life-extension and quality of life. In some cases, patients may live many months or even years with metastatic melanoma (depending on the aggressiveness of the treatment). Metastases to skin and lungs have a better prognosis. Metastases to brain, bone and liver are associated with a worse prognosis.

There is not enough definitive evidence to adequately stage, and thus give a prognosis for ocular melanoma and melanoma of soft parts, or mucosal melanoma (e.g. rectal melanoma), although these tend to metastasize more easily. Even though regression may increase survival, when a melanoma has regressed, it is impossible to know its original size and thus the original tumor is often worse than a pathology report might indicate.

Epidemiology

thumb|325px|[[Age adjustment|Age-standardized ''incidence'' rate of melanoma of the skin per 100,000 inhabitants in 2008.]]

thumb|325px|[[Age adjustment|Age-standardized ''death'' from melanoma and other skin cancers per 100,000 inhabitants in 2004.]] Generally, an individual's risk for developing melanoma depends on two groups of factors: intrinsic and environmental. "Intrinsic" factors are generally an individual's family history and inherited genotype, while the most relevant environmental factor is sun exposure.

Epidemiologic studies suggest that exposure to ultraviolet radiation (UVA and UVB) is one of the major contributors to the development of melanoma. UV radiation causes damage to the DNA of cells, typically thymine dimerization, which when unrepaired can create mutations in the cell's genes. When the cell divides, these mutations are propagated to new generations of cells. If the mutations occur in protooncogenes or tumor suppressor genes, the rate of mitosis in the mutation-bearing cells can become uncontrolled, leading to the formation of a tumor. Data from patients suggest that aberrant levels of Activating Transcription Factor in the nucleus of melanoma cells are associated with increased metastatic activity of melanoma cells; studies from mice on skin cancer tend to confirm a role for Activating Transcription Factor-2 in cancer progression. Occasional extreme sun exposure (resulting in "sunburn") is causally related to melanoma. Melanoma is most common on the back in men and on legs in women (areas of intermittent sun exposure). The risk appears to be strongly influenced by socio-economic conditions rather than indoor versus outdoor occupations; it is more common in professional and administrative workers than unskilled workers. Other factors are mutations in or total loss of tumor suppressor genes. Use of sunbeds (with deeply penetrating UVA rays) has been linked to the development of skin cancers, including melanoma.

Possible significant elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs, and the degree of skin pigmentation. Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia where people tend to retain the risk profile of their country of birth if they migrate to Australia as an adult. Individuals with blistering or peeling sunburns (especially in the first twenty years of life) have a significantly greater risk for melanoma. This does not mean that sunburn is the cause of melanoma. Instead it is merely statistically correlated. The cause is the exaggerated UV-exposure. It has been shown that sunscreen — while preventing the sunburn — does not protect mice, injected with melanoma cells a day after UV exposure, from developing melanoma.

Fair and red-headed people, persons with multiple atypical nevi or dysplastic nevi and persons born with giant congenital melanocytic nevi are at increased risk.

A family history of melanoma greatly increases a person's risk because mutations in ''CDKN2A'', ''CDK4'' and several other genes have been found in melanoma-prone families. Patients with a history of one melanoma are at increased risk of developing a second primary tumour.

The incidence of melanoma has increased in the recent years, but it is not clear to what extent changes in behavior, in the environment, or in early detection are involved.

To understand how sunscreen can reduce sunburn and at the same time cause melanoma it is necessary to distinguish between direct DNA damage and indirect DNA damage. Genetic analysis has shown that 92% of all melanoma are caused by the indirect DNA damage. Although some people believe that dark-skinned people such as those of African descent cannot get sunburns, they are in fact susceptible, and should use sunscreen accordingly, as sunscreen has been proven to protect against other cancers such as squamous cell carcinoma and basal cell carcinoma.

History

Although melanoma is not a new disease, evidence for its occurrence in antiquity is rather scarce. However, one example lies in a 1960s examination of nine Peruvian mummies, radiocarbon dated to be approximately 2400 years old, which showed apparent signs of melanoma: melanotic masses in the skin and diffuse metastases to the bones.

John Hunter is reported to be the first to operate on metastatic melanoma in 1787. Although not knowing precisely what it was, he described it as a "cancerous fungous excrescence". The excised tumor was preserved in the Hunterian Museum of the Royal College of Surgeons of England. It was not until 1968 that microscopic examination of the specimen revealed it to be an example of metastatic melanoma.

The French physician René Laennec was the first to describe melanoma as a disease entity. His report was initially presented during a lecture for the Faculté de Médecine de Paris in 1804 and then published as a bulletin in 1806. The first English language report of melanoma was presented by an English general practitioner from Stourbridge, William Norris in 1820. In his later work in 1857 he remarked that there is a familial predisposition for development of melanoma (''Eight Cases of Melanosis with Pathological and Therapeutical Remarks on That Disease'').

The first formal acknowledgment of advanced melanoma as untreatable came from Samuel Cooper in 1840. He stated that the only chance for benefit depends upon the early removal of the disease ...' More than one and a half centuries later this situation remains largely unchanged.

Research

One important pathway in melanin synthesis involves the transcription factor MITF. The MITF gene is highly conserved and is found in people, mice, birds, and even fish. MITF production is regulated via a fairly straightforward pathway. UV radiation causes increased expression of transcription factor p53 in keratinocytes, and p53 causes these cells to produce melanocyte-stimulating hormone (MSH), which binds to melanocortin 1 receptors (MC1R) on melanocytes. Ligand-binding at MC1R receptors activates adenylate cyclases, which produce cAMP, which activates CREB, which promote MITF expression. The targets of MITF include p16 (a CDK inhibitor) and Bcl2, a gene essential to melanocyte survival. It is often difficult to design drugs that interfere with transcription factors, but perhaps new drugs will be discovered that can impede some reaction in the pathway upstream of MITF.

Studies of chromatin structure also promise to shed light on transcriptional regulation in melanoma cells. It has long been assumed that nucleosomes are positioned randomly on DNA, but murine studies of genes involved in melanin production now suggest that nucleosomes are stereotypically positioned on DNA. When a gene is undergoing transcription, its transcription start site is almost always nucleosome-free. When the gene is silent, however, nucleosomes often block the transcriptional start site, suggesting that nucleosome position may play a role in gene regulation.

Finally, given the fact that melanin helps protect skin cells from UV-induced damage, new melanoma prevention strategies could involve attempts to induce melanin synthesis in individuals who would otherwise get sunburns. Redheads, for example, do not tan because they have MC1R mutations. In mice, it has been shown that the melanin production pathway can be rescued downstream of MC1R.

A study published on January 27, 2011, by M. Raza Zaidi et al. shows that interferon-γ links ultraviolet radiation to melanomagenesis in mice. Using a mouse model that allowed the visual tracking and purification of melanocytes using a green fluorescent dye, data showed that UVB-induced, macrophage-enhanced interferon-γ release results in melanoma growth, proliferation and immunoevasion. Based on these results, the interferon-γ pathway can potentially serve as part of new therapeutic measures to treat patients suffering from malignant melanoma, as well as a potential preventive strategy against UV-induced radiation.

BRAF

About 60% of melanomas contain a mutation in the B-Raf gene. Early clinical trials suggested that B-Raf inhibitors including Plexxicon(R)'s vemurafenib could lead to substantial tumor regression in a majority of patients if their tumor contain the B-Raf mutation. In June 2011, a large clinical trial confirmed the positive findings from those earlier trials.

Ipilimumab

At the American Society of Clinical Oncology Conference in June 2010, pharmaceutical company reported the clinical findings of their drug ipilimumab. The study found an increase in median survival from 6.4 to 10 months in patients with advanced melanomas treated with the monoclonal ipilimumab, versus an experimental vaccine. It also found a one year survival rate of 25% in the control group using the vaccine, 44% in the vaccine and ipilimumab group, and 46% in the group treated with ipilimumab alone. However, some have raised concerns about this study for its use of the unconventional control arm, rather than comparing the drug against a placebo or standard treatment.Meaning that the drug performed better than the vaccine, although the vaccine has not been tested before and may be causing toxicity — making the drug appear better by comparison.

In June 2011, a clinical trial of ipilimumab plus dacarbazine, combined this immune system booster with the standard chemotherapy drug that targets cell division. It showed an increase in median survival for these late stage patients to 11 months instead of the 9 months normally seen. Researchers were also hopeful that perhaps 10-20% of patients could live a long time. Some serious side-effects of revving up the immune system were seen in some patients. A course of treatment costs $120,000. The drug's brandname is Yervoy.

Targeted therapies

In clinical research setting other therapies, such as adoptive cell therapy or gene therapy, may be tested. Two kinds of experimental treatments developed at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) in the US have been used in advanced (metastatic) melanoma with high success rates in terms of melanoma treatments. The first treatment involves Adoptive Cell Therapy (ACT) using TILs immune cells (Tumor Infiltrating Lymphocytes) isolated from a patient's own melanoma tumor. These cells are grown in large numbers in a laboratory and returned to the patient after a treatment that temporarily reduces normal T cells in the patient's body. TIL Therapy following lymphodepletion can result in durable complete response in a variety of setups. Up to date, the only medical center outside the USA managed to successfully implement this technology is Sheba Medical Center through "Ella Institute of Melanoma", found in Israel (objective response rates of 50%). The second treatment, adoptive transfer of genetically altered autologous lymphocytes, depends on delivering genes that encode so called T cell receptors (TCRs), into patient's lymphocytes. After that manipulation lymphocytes recognize and bind to certain molecules found on the surface of melanoma cells and kill them.

A new treatment that trains the immune system to fight cancer has shown modest benefit in late-stage testing against melanoma. Sutent may be effective for patients with metastatic melanoma.

Surveillance methods

Advances in high resolution ultrasound scanning have enabled surveillance of metastatic burden to the sentinel lymph nodes. The Screening and Surveillance of Ultrasound in Melanoma trial (SUNMEL) is evaluating ultrasound as an alternative to invasive surgical methods.

See also

List of cutaneous conditions

Seborrheic keratosis looks like melanoma but is benign

Spitz nevus

Melanotropin receptor

Slip-Slop-Slap An Australian health campaign

Basal cell carcinoma type of non-melanoma skin cancer

Squamous cell carcinoma type of non-melanoma skin cancer

Notes

External links

Category:Melanoma

be-x-old:Мэлянома bs:Melanom bg:Меланома ca:Melanoma cs:Melanom da:Modermærkekræft de:Malignes Melanom dv:މެލިގްނަންޓް މެލަނޯމާ et:Melanoom el:Μελάνωμα es:Melanoma eo:Melanomo fa:ملانوما fr:Mélanome gl:Melanoma maligno hr:Melanom it:Melanoma he:מלנומה kk:Меланома la:Melanoma malignum lv:Melanoma lt:Melanoma hu:Melanóma nl:Melanoom ja:悪性黒色腫 no:Malignt melanom pl:Czerniak złośliwy pt:Melanoma maligno ru:Меланома simple:Melanoma sr:Меланом fi:Melanooma sv:Malignt melanom te:మెలనోమా th:เมลาโนมา uk:Меланома ur:اسودینومہ zh:黑色素瘤

Shonda Schilling (born November 23, 1967 in Dundalk, Maryland) is founder of the Shade Foundation of America. She is married to professional baseball player Curt Schilling.

Biography

Personal life

Shonda graduated from Towson State College majoring in journalism, member of the Iota Delta chapter of Zeta Tau Alpha. She worked in television production for Home Team Sports in Baltimore until marrying Curt Schilling in 1992. They have four children: Gehrig (5/27/95); Gabriella (5/22/97); Grant (10/13/99); and Garrison (6/27/02). The family resides in Medfield, Massachusetts.

Skin Cancer

Schilling was diagnosed with stage 2 malignant melanoma in February 2001. A total of five surgeries left 25 scars crisscrossing her back, arms, legs and chest. The media picked up on her skin cancer scare during the 2001 World Series, when her husband Curt won the World Series co-MVP honor for the Arizona Diamondbacks. Her story was featured in People Magazine, Glamour, Family Circle, Pregnancy, Good Housekeeping and ABC's "The View." Shonda invited Good Morning America into the operating room to witness her fifth and final surgery in order to inspire others to have their skin checked and to alter their sun habits. In 2002, she accepted the Melanoma Monday national spokeswoman role with the American Academy of Dermatology (AAD). An overwhelming response from fellow melanoma survivors resulted in Shonda creating the Shade Foundation of America.

Shade Foundation of America

Shonda Schilling founded the Shade Foundation of America in 2002 with the goal of changing society's attitude towards sun exposure. The wife of major league baseball pitcher Curt Schilling, she has traveled all over the United States promoting sun-safety awareness.

Schilling’s dedication to promote sun safety has been expressed through many partnerships and appearances. In 2003, the Shade Foundation joined with the Environmental Protection Agency (EPA) to launch the annual SunWise Poster Contest in conjunction with the Arizona Diamondbacks and the Arizona Department of Health to implement sun-safety curriculum in schools. Schilling testified before the Arizona state legislatures in an effort to help pass the current law requiring schools to teach the SunWise curriculum in the state of Arizona. The launch of this partnership was heard by 20 million people through media exposure and hundreds of school principals across the country signed up to teach the SunWise program in their classrooms. Thousands of kids have learned skin cancer prevention techniques through the program by drawing a SunWise poster for the contest. When the Schillings were relocated to Boston, Shonda partnered the program with the Dana Faber Cancer Institute in Massachusetts where it continues to result in overwhelming success.

Schilling aligned the Shade Foundation with Major League Baseball and the Play it Smart When it Comes to the Sun Program in 2005, generating awareness in MLB Parks around the country and at the MLB All-Star Game in Detroit. The program continues to reach millions of Americans with a sun-safety message through media appearances with Geraldo At Large, Women's World Magazine among other local channels across the country.

Since 2005, Schilling has participated in running the Boston Marathon every year to raise money for the Shade Foundation. She also ran the PF Chang's Rock N Roll Marathon in 2005 on behalf of the Shade Foundation.

Schilling’s involvement with the Shade Foundation has garnered intense media attention since its inception. The Schilling family appeared in a public service print advertisement promoting sun-safety in Sports Illustrated's popular swimsuit issue as well as a television PSA that aired in New England and around the country. Through all of Schilling’s hard work, she has been recognized for her commitment to the community and promoting sun safety numerous times. Shade’s partnership with the EPA earned Shonda and the Shade Foundation the "Excellence in Cancer Awareness" award in 2003 from the Congressional Families Program of the Cancer Research and Prevention Foundation in Washington, DC. That same year, she was presented with the Girl Scout World of Humanity Award by the Arizona Cactus- Pine Girl Scout Council and in her honor they created the Shade Badge for scouts to earn. Also in 2003, Shonda accepted the Outstanding Fundraiser Award by the Association of Professional Fundraisers.

She was recognized nationally with the Speaker Thomas J. "Tip" O'Neill, Jr. Award for Public Service by the Greater Boston Federal Executive Board in 2004. That same year, the American Academy of Dermatology acknowledged Shonda's awareness efforts with an individual achievement Gold Triangle Award. She was also given the Alumni of the Year Award from Zeta Tau Alpha Sorority. In 2005, Schilling picked up an honorary doctorate degree in public service from Framingham State College. She was also presented with the exceptional women's award for community service by Boston radio station Magic 106.7. Merrimack College gave Shonda an honorary Doctor of Humane Letters degree in 2006 and that same year she was awarded the Lady Baden Powell Good Scout Award by the Boston Minuteman Council. Schilling continues to serve as a commencement speaker at high school and college graduations.

The Wellness Community-Greater Boston recognized Schilling with the 2007 Gilda Radner Award as an individual who demonstrated courage, determination and hope in the face of cancer. She was named host of Facing Cancer Together, a television program produced by the Wellness Community which aired on cable stations around the country. The Massachusetts Interscholastic Athletic Association presented her with the 2007 Partners in Prevention "Making a Difference" Award during the 11th Annual MIAA Wellness Summit held in Milford, MA.

Work with the ALS Association

Shonda and Curt have been active with the [ALS Association] since 1992 in developing public awareness and fundraising campaigns to improve the services of the ALS Association. Both have appeared in numerous public service announcements featuring Curt's Pitch'n to Win campaign that joins the ALS Association and Shaw's Supermarkets in which people can donate $1.38 or $3.38 to benefit the ALS Association. Together they have donated and raised more than $9 million for ALS. Shonda serves on the Board of Directors for the Philadelphia, Arizona and Massachusetts chapters. She represents ALS at numerous functions including lobbying in Washington D.C. for government funding and before the Food and Drug Administration to get the first trial drugs approved. Shonda regularly visits ALS patients, their family members and caregivers, and is involved in helping with a variety of events associated with ALS.

She chaired the "The Shonda Schilling Say It with Flowers" Luncheon in Arizona which raised more than $250,000 spanning three years (2002–04). When the Schillings relocated to Boston, Shonda and Dawn Timlin, wife of Red Sox pitcher Mike Timlin, implemented the “Say it with Flowers” campaign in the Boston area which raises over $200,000 annually to benefit the ALS.

The Schilling family participated in ALSA's National ALS Awareness Month public service announcement in 2004 and received the “Telly Award” for excellence in a national television commercial. Schilling and her husband received the 2002 Catfish Hunt Award from the North Carolina Chapter of the ALS Association and she was also presented the All-Star Award by ALSA. In 2001, ALS Association National Office presented Shonda with the Lawrence A. RAND Award recognizing her nationally for continued service and dedication.

References

Category:1967 births Category:Living people Category:Skin cancer survivors Category:American health activists Category:Towson University alumni

Ian George Brown (born 20 February 1963 in Warrington) is an English musician, best known as the former lead singer of the alternative rock band The Stone Roses. Since the break-up of the Stone Roses he has pursued a solo career. His latest studio album ''My Way'' was released on 28 September 2009.

Biography

Early life

Brown was born in Warrington, England in 1963. His father, George, was a joiner and his mother Jean worked as a receptionist in a paper factory. When he was 5, Brown's family moved to Timperley, along with his brother and sister, as a karate-obsessed admirer of Muhammad Ali, George Best and Bruce Lee. He was educated at Park Road County Primary Infant and Junior School and then Altrincham Grammar School for Boys. His interest in music was inspired by the punk movement, specifically the bands Sex Pistols, The Clash and Manchester band Slaughter & The Dogs. Brown and original Stone Roses bassist Pete Garner attended the recording of the Clash single "Bankrobber" in Manchester.

Stone Roses

Brown's music career began in 1980, playing bass guitar in band with John Squire and Simon Wolstencroft. They eventually became The Patrol, with Andy Couzens on vocals. The band soon split up, with Brown selling his bass to buy a scooter. Brown moved to Hulme, and attended northern soul "all-nighters" across the north of England in the early 1980s as the scene faded. Around this time, Brown met soul legend Geno Washington, who told him, "You should be a star". In 1983 Brown joined The Waterfront as co-vocalist, the band that would evolve into The Stone Roses.

The Stone Roses became one of the biggest bands of the late 1980s and early 1990s, with their debut album voted the best British album of all time in 2004. The band's second album, ''Second Coming'', received a mixed reaction, and after several changes of line-up, the band split up in October 1996.

Solo career

After a break from music in Morocco, Brown established his solo career with the debut solo single "My Star", which was released in the UK on 12 January 1998. The debut album ''Unfinished Monkey Business'' followed on 2 February 1998. The album was produced and financed by Brown, and featured ex-Roses members Mani, Nigel Ipinson, Aziz Ibrahim and Robbie Maddix. The album sold over 300,000 copies.

Brown toured in Summer 1998 with a band that included Ibrahim, Inder Mathura (percussion), Simon Moore (drums), and Sylvan Richardson (bass), including performances at the Glastonbury Festival and the V Festival.

His second album, ''Golden Greats'', was released by Polydor Records 1999. It featured more electronic instrumentation and earned high critical acclaim. For his third studio album ''Music of the Spheres'' Brown sought outside production help for the first time, hiring the services of songwriter and producer Dave McCracken who would go on to become a regular collaborator. He toured the US for the first time as a solo artist in support of the album.

Brown's fourth solo album, ''Solarized'', was released in the UK on 13 September 2004, and was the first to be released under the revived Polydor imprint Fiction Records. When his new Fiction A&R; Jim Chancellor was asked in HitQuarters what contribution he makes to Brown's records he said, "There's not as much to do. Ian is very much the master of his own records."

Since the break-up of the Stone Roses in 1996, Brown has released six solo albums and fourteen UK Top 40 singles. He has sold out seven UK tours, and appeared three times at the Glastonbury Festival, including headlining The Other Stage in 2005. He has also appeared five times at V Festival since 1998. Brown has also regularly appeared at T in the Park and Oxegen festivals and played the Move festival in 2002 at Lancashire Cricket Ground.

Brown had a cameo role in the 2004 film ''Harry Potter and the Prisoner of Azkaban'.

For the 2005/6 season, Brown was the shirt sponsor of London Commercial Division football team Chiswick Homefields, the players wearing an 'IB – The Greatest' logo on their chests.

At the 2006 ''NME'' awards, Brown was presented with the "Godlike Genius" award and in 2007 was given the ''Q'' "Legend" Award.

In September 2007, Brown released his fifth studio album, ''The World is Yours''. The album represented a more political approach in his music, particularly the anti-war track "Illegal Attacks", which featured Sinéad O'Connor. The album also featured former Smith bassist Andy Rourke and Paul Ryder of Happy Mondays.

''My Way'', his sixth solo album, was released in September 2009. It was recorded at London's Battery Studios with producer Dave McCracken; the first single, "Stellify", was released 21 September 2009.

Brown has collaborated several times with UNKLE, appearing on "Be There" in 1999 and on "Reign" on the 2003 album ''Never, Never, Land'', which was also released as a single.

Awards and achievements

Brown has won numerous awards in his career, in recognition of his work as a solo artist and his work with The Stone Roses. The awards he has won are as follows:

;The Stone Roses

1997 ''The Stone Roses'' reached No. 5 in ''The Guardian'''s 100 Best Albums Ever poll

1998 ''The Stone Roses'' reached No. 4 in ''Q'' magazine's 100 Best Albums Ever poll

2004 ''The Stone Roses'' reached No. 1 in ''The Observer'''s 100 Best British Albums Ever poll

2006 ''The Stone Roses'' reached No. 1 in the ''NME'' writers 100 Best British Albums Ever poll

2006 ''The Stone Roses'' reached No. 7 in ''NME'' fans 100 Best Albums Ever poll

;Solo

2002 Muso Awards Best Single ("Whispers")

2002 NME Awards Best Solo Artist 2006 NME Awards Godlike Genius Award 2007 Q Awards Legend Award 1999, 2000, 2002, 2006, 2009 – nominated for Best British Solo Artist at the Brit Awards

Discography

In the UK Ian Brown as a Solo Artist and with The Stone Roses has sold over a Certified 1.7 Million Albums

Albums

align="center" ''Golden Greats (Ian Brown Album) ''Music of the Spheres (Ian Brown album) ''Solarized'' ''The World Is Yours (Ian Brown album) ''My Way (Ian Brown album) ''The Greatest (Ian Brown album) The Greatest Promos

Year !! Studio Albums !! UK Album Chart	UK !! Certification
1998	''Unfinished Monkey Business''	>UK: Gold
1999	Golden Greats'' ||	14	British Phonographic Industry>UK: Gold
2001	Music of the Spheres'' ||	3	British Phonographic Industry>UK: Gold
2004	|	7	British Phonographic Industry>UK: Gold
2007	The World Is Yours'' ||	4	–
2009	My Way'' ||	8	–
Year !! Remix Albums !! UK Album Chart	UK !! Certification
2002	''Remixes of the Spheres''	87
Year !! Compilation Albums !! UK Album Chart	UK !! Certification
2004	Under the Influence (compilation album)>Under The Influence	–
2005	The Greatest'' ||	5	British Phonographic Industry>UK: Gold
2005	|	–	–

Singles

1998 1998 1999 1999 2000 2000 2001 2002 2004 2004 2005 2005 2007 2007 2009 2009

Title !! Year !! UK Singles Chart	UK !! Notes
"My Star (Ian Brown song)	My Star"	1998	5
"Corpses in Their Mouths	Corpses"	|	14
"Can't See Me"	|	21
"Be There (song)	Be There"	|	8	UNKLE featuring Ian Brown
"Love Like a Fountain"	|	23
"Dolphins Were Monkeys"	|	5
"Golden Gaze"	|	29
"F.E.A.R. (song)	F.E.A.R."	|	13
"Whispers (Ian Brown song)	Whispers"	|	33
"Keep What Ya Got"	|	18
"Reign"	|	40	UNKLE featuring Ian Brown
"Time Is My Everything"	|	15
"All Ablaze"	|	20
"Illegal Attacks"	|	16	Ian Brown featuring Sinead O'Connor
"Sister Rose"	|	87
"Stellify"	|	31
"Just Like You"	|

Notes

References

Larkin, Colin (ed.) (1998) ''The Virgin Encyclopedia of Indie & New Wave'', Virgin Books, ISBN 0 7535 0231 3

Robb, John (2001) ''The Stone Roses and the Resurrection of British Pop'', Random House, ISBN 0-09-187887-X

External links

The Definitive Ian Brown Discography

Category:1963 births Category:English male singers Category:English rock singers Category:English songwriters Category:Living people Category:People from Warrington Category:People from Altrincham Category:The Stone Roses members Category:E1 Music artists Category:Polydor Records artists Category:People educated at Altrincham Grammar School for Boys

da:Ian Brown de:Ian Brown es:Ian Brown fr:Ian Brown ko:이언 브라운 it:Ian Brown he:איאן בראון ja:イアン・ブラウン no:Ian Brown pl:Ian Brown pt:Ian Brown ru:Браун, Иэн sk:Ian Brown fi:Ian Brown uk:Іен Браун