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(American Journal of Pathology. 1999;154:745-754.)
© 1999 American Society for Investigative Pathology

Regular Articles

Down-Regulation of HLA Class I Antigen-Processing Molecules in Malignant Melanoma

Association with Disease Progression

Toshiro Kageshita* , Shunji Hirai* , Tomomichi Ono* , Daniel J. Hicklin{dagger} and Soldano Ferrone{dagger}

From the Department of Dermatology,* Kumamoto University School of Medicine, Kumamoto, Japan, and the Department of Microbiology and Immunology,{dagger} New York Medical College, Valhalla, New York

Expression of the proteasome subunits LMP2 and LMP7, the MHC-encoded transporter subunits TAP1 and TAP2, and HLA Class I antigens was examined by immunoperoxidase staining in 10 nevi and 98 melanoma lesions (60 primary and 38 metastatic), because these molecules play an important role in the presentation of melanoma-associated peptide antigens to cytotoxic T cells. LMP2 was less frequently expressed than LMP7 in primary and metastatic melanoma lesions. TAP1, TAP2, and HLA Class I antigen expression was more frequently (P < 0.05) down-regulated in metastatic than in primary melanoma lesions and in nevi. A synchronous TAP1, TAP2, and HLA Class I antigen down-regulation was observed in 58% of primary and 52% of metastatic lesions. TAP and HLA Class I antigen down-regulation in primary lesions was significantly associated with lesion thickness, stage of disease, reduced time to disease progression, and reduced survival. These results suggest that TAP down-regulation plays a role in the clinical course of malignant melanoma, probably by providing melanoma cells with a mechanism to escape from cytotoxic T lymphocyte recognition during disease progression.




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