Dictionary - Cancer: Melanoma - The Human Protein Atlas

DICTIONARY

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On the welcome page of the dictionary, four major sections are shown: Normal tissues, Cancer, Cell structure and Protein expression. Below the image of each section are links to introductory texts for i) normal tissue histology, ii) hallmarks of cancer, and iii) cell structure overview. For the cancer-section there is also a link to current cancer statistics (incidence, survival, etc) for Sweden and the rest of the world. Below the Protein expression section there is a list of genes with links to examples of different protein expression patterns. Within each section there are direct links to histology descriptions of different tissue types and tumor forms as well as descriptions of cell structures.

For the 'Tissue & cell types' and 'Tumors' sections, tissue-slides stained with hematoxylin and eosin (HE) are shown at three different levels of magnification. On the top level, an overview of the whole tissue-sample is shown with boxes in black indicating where zoomed-in representative parts of the tissue are available for viewing. Clicking on these boxes will zoom in on that part to show tissue structures, cells and features in greater detail. Throughout these sections, arrows indicate relevant tissue structures, cell-types and other features.

For the 'Cell structure' section, immunofluorescent images of formaldehyde-fixed cell lines are shown. The various cell structures that are demonstrated are always shown in the green channel using an antibody found in the Human Protein Atlas. The antibody name is linked to the subcellular location summary page of the target gene. The other channels: nucleus, microtubules and endoplasmic reticulum, are always shown in the blue, red and yellow channels, respectively. The channels can be toggled on and off by clicking on the respective coloured button above the image. When applicable, the immunofluorescent images are complemented by immunohistochemically stained cells where the location of the particular cell structure is shown in brown.

For the 'Protein expression' section, tissue slides representing both normal and cancer tissue have been stained using immunohistochemistry to visualize various protein expression patterns. Antibodies have been selected to demonstrate the expression patterns of well-known proteins and to reflect antibodies used in clinical diagnostics to determine the nature of a given cancer. For certain antibodies the corresponding protein expression pattern is shown in both normal and cancer tissues. For each exemplified protein there is a short descriptive text including also the clinical usefulness of the corresponding antibody.

A common feature for all sections is that a general descriptive text about the tissue, tumor-type, cell structure or protein/antibody is provided when browsing a particular topic.

Dictionary > Cancer > Melanoma

Female, 46 years, Nodular malignant melanoma, tumor thickness 3,7 mm

Melanoma

Malignant melanoma is the leading cause of skin-related death in Caucasians, but rare in populations with darker pigmented skin color. The incidence has increased dramatically during the last decades, with an almost four-fold increase in the Nordic countries in the time period 1964-2003. The increased incidence represents in part different sun exposure habits in the population, but hereditary risk factors including skin type are also important. Short intermittent exposure with sunburns appears to be the main risk factor. Other important risk factors include the number of melanocytic nevi and the number of dysplastic melanocytic nevi.

Patients that present with an advanced tumor stage at time for diagnosis and patients with relapse of melanoma after surgical removal generally have a poor prognosis. In patients diagnosed with localized disease the most important prognostic indicator is the thickness of the tumor at the time of diagnosis. The tumor thickness is measured in mm (according to a system initially described by Breslow) and is the dominating parameter for determining the tumor stage (T-stage) of melanoma. Other prognostic factors include mitotic rate and ulceration as well as clinical factors such as patient age, gender and the anatomic site of the primary tumor. In Sweden, the 5-year melanoma specific survival rate is 98% for patients in stage IA (tumor thickness <1mm and without ulceration and 49% for patients in stage IVB (tumor thickness >4 mm and with ulceration).

Primary cutaneous malignant melanoma is thought to develop in a multi-step process. Precursor lesions, such as dysplastic melanocytic nevi develop into a melanoma in situ stage and further into invasive melanoma and eventually metastatic melanoma. Invasive malignant melanoma is traditionally divided into four principal histopathological subgroups based on the microscopical appearance: superficial spreading melanoma (SSM), nodular malignant melanoma (NMM), lentigo maligna melanoma (LMM) and acral lentiginous melanoma (ALM).

The histopathological features of malignant melanomas vary widely. A typical feature, often facilitating the diagnosis of melanoma, is the occurence of a pagetoid growth pattern. Patgetoid growth pattern is characterized by growth of melanoma cells in the upper layers of the epidermis (as opposed to the localization of normal melanocytes in basal layers of the epidermis). The melanoma cells can be large and rich in cytoplasm, small or even spindly. In a subset of melanomas there are areas with abundant melanin and in other melanomas melanin pigment is scarce or absent. Tumor cell nuclei are enlarged, often with a prominent nucleolus and mitoses are present at a variable degree. Immunohistochemistry is often used to distinguish malignant melanoma from other tumor types. Traditionally, antibodies towards different S-100 proteins have been used as immunohistochemical markers of melanocytes, however, antibodies also stain positive in e.g. Langerhans cells and nerve fibers. Other markers such as Melan-A (MART-1) and tyrosinase (TYR), stain melanocytes more specifically and are useful to determine if a tumor is of melanocytic origin. Proliferation markers are also widely used in the differential diagnostics of melanocytic lesions with uncertain malignant potential. The most accepted markers for cells active in the cell cycle are antibodies binding to Ki-67 (MKI67) and the presence of Ki-67 positive melanocytic cells is often used in routine pathology to distinguish malignant melanoma from benign melanocytic tumors.

Normal tissue: Skin