Prognostic impact of cancer-testis antigen expression in primary cutaneous melanoma

9004 Background: Cancer-testis antigens (CTAg) are epigenetically regulated molecules expressed in many cancers including melanoma. Although functional studies are limited, they are often immunogenic making them attractive targets for immunotherapy. In normal tissues expression is restricted to germ cells and a small range of other tissues such as trophoblast. Previous studies have shown that CTAg expression increases with disease progression. We investigated whether the expression of three CTAgs, against which vaccines have been developed, may have prognostic significance in early stage melanoma. Methods: 233 AJCC Stage II melanomas were analyzed for expression of MAGE-A1, MAGE-A4 and NY-ESO-1 by immunohistochemistry. The relationship between CTAg expression, clinico-pathological features and relapse free survival (RFS) from initial diagnosis were correlated. Mutivariate analysis using known prognostic factors and CT Ag expression in the model were used to calculate hazard ratios. Results: All three CTAg were significantly co-expressed with each other (P=0.0001). RFS was reduced if tumors expressed any of these CTAgs (CTAg+ve). Median RFS for patients with CTAg+ve tumors was 45m versus 72m for those with CTAg-ve tumors (P=0.008, logrank test). Univariate analysis demonstrated that the impact of CTAg expression on RFS was comparable in magnitude to ulceration, Breslow thickness and mitotic rate, currently accepted prognostic factors. Multivariate analysis demonstrated CTAg expression, ulceration and thickness but not mitotic rate were independently associated with poorer RFS ( Table ). Conclusions: CTAg expression in cutaneous primary melanoma has impact on prognosis comparable to Breslow thickness ulceration and mitotic rate. Further study into their function and the impact of clinical targeting is warranted. [Table: see text] No significant financial relationships to disclose.