ABSTRACT
Gianfranco Mattia,c Nadia Fellid and Alessandra Carèe
Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Viale Regina Elena, 299-00161 Rome, Italy. aEmail: federica.felicetti@iss.it bEmail: mariacristina.errico@iss.it cEmail: gianfranco.mattia@iss.it dEmail: nadia.felli@iss.it eEmail: alessandra.care@iss.it *Corresponding author
Cutaneous melanoma is an aggressive neoplasia whose incidence is steadily increasing being the number of melanoma cases worldwide rising faster than any other cancer. Screening and early detection are still the best prognostic factors leading to 99% of favorable outcome if the primary lesion is detected very early (more than 90% survival in stage I melanomas). At the initial phases of the disease surgical excision mostly represents a defi nitive solution, but no effective therapies have been determined for advanced stages and the overall 5-year survival of metastatic melanomas remains lower than 10%. This fact gets even more aggravating, considering metastasis to distinct organs as a very early event in the progression of this disease. It is then obvious how important might be to study in depth the molecular oncogenic pathways implicated in transformation and progression in order to identify new representative markers for diagnosis, prognosis and eventually therapeutic treatments. Several melanoma biomarkers, such as the mitotic and the Ki-67 marker expression indexes, have been evaluated for their prognostic utility with promising early results (Vereecken et al. 2007); however, to date, none has been proven to be clinically useful in large-scale studies (Larson et al. 2009). Although several molecular abnormalities have been associated with melanoma progression, as the loss of AP-2 transcription factor (Huang et al. 1998) or the high mutation rate of the B-RAF oncogene (Dhomen and Marais 2007), the mechanisms underlying the differential gene expression are still largely unknown and the conventional histological classifi cation remains the best prognostic factor (Clark et al. 1984). The Clark model describes the histological changes that accompany the progression from normal melanocytes to malignant melanoma (Fig. 1).
