Abstract: |
The expression of monomorphic determinants of the histocompatibility leukocyte antigens (HLA) class I antigens by human malignant tumor cells was studied in tissue specimens of 70 primary tumor lesions obtained from patients with carcinoma of the breast (41 patients), colon (8 pa tients), urinary bladder (8 patients), and kidney (13 patients), and in samples of either synchronous or metachronous lymph node, lung, or liver mã©tastasesavailable in 44 of the patients. The frequencies of HLA class I expressor and nonexpressor tumor cells were determined by immunohistochemical staining of histolã3gica! sections of fresh frozen tissue samples with the W6/32 monoclonal antibody. The tumor cell populations in the majority of the primary lesions consisted predomi nantly of HLA-immunoreactive cells (observed in 38 of 70 patients; 54%), especially in those patients who did not have clinical evidence of metastatic disease (8 of 11 patients; 73%). Various degrees of loss of reactivity were observed in other primary lesions, although in only 8 (12%) tumors (7 of which were obtained from patients with metastatic disease), the neoplastic cells were nearly exclusively HLA-nonreactive. In contrast, the majority of metastatic lesions consisted of either predom inantly HLA-negative cells (33 of 44 specimens; 75%) or mixed popula tions (10 of 44 specimens; 23%), whereas only one metastatic lesion manifested HLA class I antigen staining in more than 70% of its tumor cells (P = 0.0005). Intravascular clusters of tumor cells consisted pre dominantly of HLA class I nonexpressors. The observed patterns of distribution of HLA expressors and nonexpressor tumor cells are com patible with the notion that HLA-negative cells in human carcinomas manifest a selective advantage with regard to metastatic progression and growth. The suppressed expression of major histocompatibility complex class I antigens on metastatic cells may lead to failure of presentation of cell surface tumor specific epitopes to host cytotoxic T-lymphocytes. Such a process would enable tumor cells to evade host immune responses and would promote and enhance cell dissemination and metastatic growth. © 1991, American Association for Cancer Research. All rights reserved. |
Keywords: |
immunohistochemistry; human tissue; major clinical study; neoplasms; antigen expression; metastasis; breast cancer; breast; colonic neoplasms; breast neoplasms; bladder cancer; kidney neoplasms; immunoenzyme techniques; antibodies, monoclonal; kidney; antigens, neoplasm; carcinoma, renal cell; hla antigen class 1; hla-c antigens; neoplasm metastasis; bladder neoplasms; kidney cancer; colon; hla-a antigens; hla-b antigens; bladder; neoplasm circulating cells; human; male; female; priority journal; article; support, u.s. gov't, p.h.s.
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