COMPARATIVE DECREASES IN TYROSINASE, TRP-1, TRP-2, AND PMEL 17 SILVERANTIGENIC PROTEINS FROM MELANOTIC TO AMELANOTIC STAGES OF SYNGENEIC MOUSE CUTANEOUS MELANOMAS AND METASTASES/

Malignant cutaneous melanomas and metastases were taken directly from in situ lesions of genetically identical (C57BL/6 strain) Tyr-SV40E tr ansgenic mice, and samples mere analyzed by Western immunoblotting wit h antisera specific for the COOH terminus of each of four melanocytic proteins, These were tyrosinase, TRP-1, TRP-2, and Pmel 17/silver. Of the 13 melanomas examined, there were 5 melanotic primary tumors, 5 am elanotic primary tumors, and 3 amelanotic metastases. The melanotic tu mors expressed all of the markers to some extent, In contrast, the ame lanotic tumors lacked detectable levels of one, two, or three of the p roteins, except for an apparently amelanotic tumor sample in which all were expressed, but in which some melanotic cells were likely to have been present, Thus, despite some variability, there is clearly a down ward trend in the presence of these proteins as the tumors become amel anotic, a pigmentary change associated with ongoing malignant progress ion, In the amelanotic tumors, tyrosinase was most often deficient, wh ereas TRP-2 was most often persistently expressed, These results, obta ined from melanomas of syngeneic origin, indicate that tumors in the r elatively early stages of malignancy might be more responsive than lat er-stage tumors to immunotherapy involving an ensemble of antigenic pe ptides of the tested gene products, Moreover, TRP-2 peptides may be es pecially useful for therapeutic intervention at the later stages.