The establishment of the diagnosis of cutaneous malignant melanoma (CMM) always calls for histopathological confirmation.\r\nFurther to the recognition of the CMM aspects, immunohistochemistry is helpful, in particular, in determining the size of the\r\nreplicative compartment and the activity in each of the cell cycle phases (G1, S, G2, M). The involvement of cancer stem cells and\r\ntransient amplifier cells in CMM genesis is beyond doubt. The proliferation activity is indicative of the neoplastic progression and\r\nis often related to the clinical growth rate of the neoplasm. It allows to distinguish high-risk CMM commonly showing a high\r\ngrowth rate, from those CMMs of lower malignancy associated with a more limited growth rate. The recruitment and progression\r\nof CMM cells in the cell cycle of proliferation depend on mitogen-activated protein kinase (MAPK) pathway and result from a loss\r\nof control normally involving a series of key regulatory cyclins. In addition, the apoptotic pathways potentially counteracting any\r\nexcess in proliferative activity are out of the dependency of specific regulatory molecular mechanisms. Key molecular components\r\ninvolved in the deregulation of the growth fraction, the cell cycle phases of proliferation, and apoptosis are presently described in\r\nCMM.
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