The candidate is a diagnostic surgical pathologist whose immediate research goals are the detection and molecular characterization of circulating tumor cells (CTC) and micrometastases in solid tumors, especially in malignant melanoma (MM). His long term goals are the 1) development of these molecular tests into clinically relevant prognostic markers and 2) an in depth analysis of the mechanisms of metastases in solid tumors. Memorial Sloan-Kettering Cancer Center has the clinical and laboratory facilities appropriate for the development of junior faculty members into independent researchers, and for the conduct of this type of research. There is a need for better prognostic markers in advanced MM. The objectives of this proposal are to assess the prognostic significance of CTC and bone marrow (BM) micrometastases in patients with advanced melanoma (i.e patients with melanoma >4mm thickness, with lymph node or distant metastases). Blood and BM from 250 patients with advanced melanoma who were rendered surgically free of disease will be tested for CTC and micrometastases using reverse transcriptase po1yrnerase chain reaction (RT PCR) for the presence of tyrosinase, MART1/Melan-A and GAGE mRNAs. The test data will be correlated with outcome and other clinico-pathologic parameters - The investigators will also study the variation in blood RT PCR results in relation to serial sampling and its prognostic significance. The expression of these markers will be also studied in the primary tumors and metastatic tissue deposits by immunohistochemistry and RT PCR. This latter tissue data will be correlated with the RT PCR tests for CTC and BM micrometastases in order to study how these markers are modified during the metastatic process. This will increase our understanding of the metastatic process in MM, and provide new prognostic markers aimed at better stratifying and therefore more accurately treat MM patients.
