MOLECULAR ONCOGENE MARKERS AND THEIR SIGNIFICANCE IN CUTANEOUS MALIGNANT-MELANOMA

Background: Oncogenes and other molecular tumor markers that predict t umor aggressiveness may allow individualization and optimization of su rgical therapy of intermediate-thickness malignant melanoma. We examin ed the expression of selected markers, including the HLA-DR antigen, t he heat shock protein-70 (HSP-70), and the c-myc oncogene in primary m elanoma and regional nodes and related these findings to metastatic po tential and survival. Methods: Forty patients with primary melanoma (1 .5-4.0 mm) were studied, all of whom lad prophylactic lymph node disse ction and were followed for 18 months to 7 years. The primary tissue a nd nodes were examined using immunohistochemical techniques for the pr esence of HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene. Results: Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients who had elective node dissection . HLA-DR antibody stained the primary tumor in 10 patients (25%), but there was no correlation with survival in this group. HLA-DR antibody stained the stroma and cellular infiltrates surrounding the primary tu mor in 28 of 40 patients; in this group there was a correlation of HLA -DR staining of the peritumoral stroma with improved survival overall. HLA-DR staining of the peritumoral stroma also influenced survival wh en patients were stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of patients, who were also shown to have sig nificantly improved survival when compared with those whose primary tu mor did not stain with HSP-70. C-myc was expressed in the primary tumo r in 25%, but showed no correlation with survival. None of these prote ins correlated with or predicted the presence of nodal metastases. Con clusion: We conclude that the use of specific molecular-oncogene marke rs in intermediate thickness primary melanoma may identify patients at high risk for conventional treatment failure and reduced survival who may profit from more aggressive surgery, adjuvant therapy, or both.