IL-33 Prognostic factors in melanoma.

Cutaneous Melanoma (CM) has been the subject of many investigators since this neoplasm shows a dramatic world-wide increase in incidence since the past 25 years. Although CMs, harboring well-defined growth phases, are an ideal model to study tumor progression, most studies up till now used extracts from whole tumors, or cell lines derived from an unknown growth phase, and do not allow to study the chronology of genetic alterations. Therefore, we used microdissection to analyse tumor progression, such as oncogene activation in the distinct growth phases of CM. In this study, we found that Ras oncogene activation is an important mechanism in the initiation and progression of CM and that some mutations preferentially occur in specific growth phases. A clonal relationship could be confirmed between the different tumor progression stages of CM and even between primary CM and associated nevi. We also detected a novel mutation in the N-ras gene in 10% of the CM. Melanomas with this mutation were significantly thinner and identified a group with better prognosis than melanoma patients with the classical Ras mutations or even without Ras mutations. Our results show that tumor progression occurs stepwise in CM and that different mechanisms are responsible for different steps in the development of CM. We also showed that oncogene mutations can also inhibit tumor formation, and in our case contribute to a better prognosis for these melanomas. [ABSTRACT FROM AUTHOR]