Molecular pathways supporting the proliferation staging of malignant melanoma (review)

The clinical diagnosis of cutaneous melanoma always calls for histological confirmation. In addition to the recognition of the classic aspects of the neoplasm, immunohistochemistry is determinant, in particular in the assessment of the size of the replicative compartment. Generally, the proliferation rate is indicative of the neoplastic progression and is related to the clinical growth rate of the neoplasm. It allows to distinguish high risk melanomas showing a high growth rate from those of lower malignancy associated with a restricted growth rate. In melanoma, the recruitment and progression of neoplastic cells in the cell cycle of proliferation have lost some of their controls that are normally processed by a series of key regulatory molecules. In addition, the apoptotic pathway counteracting any hyperproliferative activity is released of the dependency of specific regulated molecular mechanisms. This review summarizes the current knowledge on key molecular components involved in the deregulation of the growth fraction, cell proliferation and apoptosis in melanocytic neoplasms. The implication of cyclins and of the mitogen-activated protein kinase pathways are scrutinized. The involvement of neoplastic stem cells in the metastatic process is also discussed.