We studied by immunohistochemistry the HLA-allelic, β2-microglobulin, and TAP-1 expression in primary breast carcinomas and related lymph node metastases. Thirty-three of the primary tumors and 44% of the lymph node metastases had a complete HLA class I loss. The higher incidence of antigenic loss in metastatic tumors suggests that recognition of HLA class I antigens by the host immunity could have an important role in the metastatic evolution of breast cancer. We observed a simultaneous defective expression of all three components involved in HLA class I expression. Since the controlling genes of heavy chain and TAP-1 are located in different chromosome than β2-microglobulin, it could be that a common factor exists regulating HLA class I antigenic expression. Five of 25 (20%) primary and metastatic tumors from HLA-A2-positive individuals also had a selective loss. The high incidence of HLA class I loss in breast cancer patients shows that adjuvant immunotherapy to induce HLA class I expression could be of value in a subgroup of patients.

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