Streamlining Molecular Pathobiology of Malignant Melanoma

Abstract

Currently, regular histopathology and immunohistochemistry are commonly taken for granted in the diagnosis of Cutaneous Malignant Melanoma (CMM). In addition, attempts at molecular diagnosis in dermatopathology have benefited from advances in pathobiology genomics and proteomics. They provide utmost information for optimal patient care. Sensitive techniques detect specific DNA and RNA sequences, and molecular methods were refined in the field of polypeptides. This review aims at covering on an overall glance about molecular genetics available as diagnostic supports in CMM. Laboratory methods have disclosed and highlighted some pathogenic pathways of atypical melanocytic neoplasms with particular emphasis on the activation of the Mitogen-Activated Protein Kinase (MAPK) signalling pathway (including BRAF and KIT) during the initiation step of the neoplasms. Many familial CMM contain mutations of the tumor suppressor gene p16 or CDKN2A. In addition, mutations in p53 are found in distinct CMM types. Many CMM are likely related to a variety of common low penetrance genes. Molecular dermatopathology represents a promising tool for both research and diagnosis. Knowledge of tumor mutation status is becoming increasingly important. The expected benefit of molecular dermatopathology tends to ultimately improve the targeted patient management. Such method evolution points to a need for improving the routine training requirements for dermatopathologists involved in cancer diagnostic responsibilities.

Simulants of malignant melanoma

“…Molecular biology opens novel methods in the diagnostic field of skin melanocytomas. 49 At present, fluorescence in situ hybridization (FISH) testing was used in lesions with borderline morphologies 50 , 51 showing molecular complexity and a variety of mutations. The chromosomal G banding testing will probably provide superior information to FISH for classifying skin melanocytomas and other AMN.…”

Functional Regulation Triad of Mitosis, Apoptosis and Thigmotropism of Survivin in Cutaneous Malignant Melanoma

“…In CMM cells, this agent protects against caspase-independent apoptosis [19]. The pro-apoptotic activity of dominant-negative survivin mutants in CMM cells reduces CMM tumor growth [7,20,21].…”