Antiapoptotic bcl-2 and bcl-xL in advanced malignant melanoma

Apoptosis is an important cofactor in the pathogenesis of a plethora of mal ignancies. However, little is known about modulation of the expression of b et gene family in melanocytic turners. To determine the role of bcl-2, bcl- x: and bax: in melanocytic tumors we investigated the differential expressi on of these genes via RT-PCR in tissue samples from human benign nevi, prim ary melanomas and melanoma metastases in comparison with normal skin. Bcl-2 was strongly expressed in 14/16 metastases (87.5%), whereas only 7/13 prim ary melanomas (53%), 7/15 nevi (46%) and 7/16 normal tissue samples (43%) s howed expression of bcl-2 (P < 0.05). There was a strong indication of a co rrelation between tumor thickness and bcl-2 expression in nodular malignant melanomas, Expression of bcl-x; was found in 16/16 melanoma metastases (10 0%), 11/13 primary melanomas (84%), 12/15 nevi (80%) and 10/16 normal tissu e samples (62%) (P < 0.05). Bcl-xL expression increased from primary melano ma to melanoma metastases, whereas bcl-xS showed a decreasing expression le vel during melanoma progression. No differences in bax: expression were see n between melanoma metastases, primary melanoma, nevi and normal tissue. Im munohistochemical investigations of another 53 tissue samples showed simila r results. Our results strongly indicate that bcl-2 and bcl-xL gene express ion increases with progression of malignant melanoma, Bcl-2 and bcl-xL expr ession could reflect an increased malignant potential caused by an inhibiti on of apoptosis and growth advantage for metastatic melanoma cells.