EXPRESSION OF RASGTPASE ACTIVATING PROTEIN IN BASAL-CELL CARCINOMA OFTHE SKIN

The ras proto-oncogene, a key component in the signal transduction cas cade of activated growth factors, is involved in multiple tumor types, including basal cell carcinoma (BCC). rasGTPase activating protein (r asGAP), is a dual function protein in the ras signaling pathway, i.e., it downregulates activated ms via its catalytic domain, and it also p articipates in the downstream effector signaling pathway by mediating protein-protein interaction. Missense mutations presumably leading to rasGAP activation were previously detected in this gene, in a subset o f BCCs. To assess the role of rasP21 and rasGAP in BCC tumorigenesis, we performed an immunohistochemical analysis of 48 BCCs, of which 45 w ere of the circumscribed variant (indolent-growth tumors) and the rema ining 3 (2 morpheaform, 1 infiltrative), were aggressive-growth varian ts. rasGAP overexpression was demonstrated in 7 of 48 BCC cases, i.e., in 4 (8.8%) of 45 indolent-growth cases and in all of the 3 aggressiv e-growth cases. We detected tumor-specific reduction of rasP21 levels in 5 (11.1%) of 45 cases, There was no overlap between the tumors disp laying rasGAP and rasP21 alternations and a high proliferation index, as assessed by Ki-67 staining, except for one case of aggressive-growt h variant. We conclude that rasGAP overexpression is associated with B CC tumorigenesis in a ras-independent manner, is not reflective of the proliferation status of the tumor, and is more characteristic of aggr essive-growth BCCs.