KBA62 and PNL2: 2 new melanoma markers-immunohistochemical analysis of 1563 tumors including metastatic, desmoplastic, and mucosal melanomas and their mimics.

Identification of metastatic melanoma can be difficult because of its great morphological variation and mimicry of a wide variety of other tumors. The more melanoma specific melanoma markers: melanA/MART-1, HMB45, and tyrosinase, used in addition to S100 protein, each have limitations in sensitivity and specicifity. In this study, we evaluated two newer melanoma markers: monoclonal antibodies KBA62 and PNL2 to yet unidentified antigens, using a large panel of metastatic melanomas (n=214), desmoplastic melanomas (n=34), GI mucosal melanomas (n = 54), benign nevi (n=27), clear cell sarcomas (n = 16) and non-melanocytic tumors (n=1218). Immunoreactivity for KBA62 and PNL2 was found in all pigmented nevi and in 86% and 90% of metastatic melanomas, respectively. Mucosal melanomas showed a similar rate of PNL2 immunoreactivity, but somewhat less frequent KBA62-positivity (72%). In addition, KBA62 was found to be a sensitive diagnostic marker for desmoplastic melanoma (28/34; 82%), whereas PNL2 was only rarely positive (2/34; 6%). KBA62 positive normal tissues included pericytes, vascular and parenchymal smooth muscle, basal cells of complex epithelia, including myoepithelia, while PNL2 labeled only melanocytes and neutrophils. Among non-melanocytic tumors, KBA62-positive were nodular fasciitis, leiomyoma, and leiomyosarcoma, gastrointestinal stromal tumor, benign and malignant nerve sheath tumors, synovial sarcoma, and subsets of various carcinomas, especially those with squamous cell/stratified epithelial differentiation. PNL2-positivity in non-melanocytic tumors was more restricted but occurred consistently in angiomyolipoma and other PEComas, and in chronic myeloid leukemia tissue infiltrates. KBA62 may assist in identification of desmoplastic melanomas, but its widespread occurrence in non-melanomas limits utility. PNL2 is highly specific for melanomas, but lacks reactivity with desmoplastic melanomas. It is also an excellent supplementary marker for PEComas at various sites.