Novel biomarkers in malignant melanoma.

Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Melanoma progression is well defined in its clinical and histopathological aspects (Breslow's index, tumour size, ulceration, or vascular invasion), which also give hints to prognosis of the patient. Use of molecular markers should therefore give additional information which cannot be determined by routine histopathology. Markers showing only a correlation to Clark level or tumour size are not useful. Several molecules influencing invasiveness and metastatic dissemination of melanoma have been identified. Expression of these molecules has been studied in primary melanoma and correlated with prognosis. Moreover, several tumour suppressors and oncogenes have been shown to be involved in melanoma pathogenesis, including CDKN2A, PTEN, TP53, RAS and MYC, but have not been related to melanoma subtypes or validated as prognostic markers. In the past, in melanoma, an increase in the number of positive tumour cells for Ki67 (detected by Mib1), cyclin A, cyclin D, MMP-2, integrins beta1 and beta3 or osteonectin were considered as factors of poor prognosis as well as the decrease in p16, p27, and Melan A. However, only a small subset of these proteins has a prognostic value independent of tumour thickness. The recent development of high-throughput technologies analyzing global molecular profiles of cancer is bringing up previously unknown candidate genes involved in melanoma, such as Wnt-5A and B-raf. Here, recently published data related to new genes involved in melanoma pathogenesis, which may represent important biomarkers for the identification of genetic profiles or indication of progression of melanoma, are reviewed.