HLA‐DRB alleles are differentially expressed by tumor cells in breast carcinoma

• Published in: International journal of cancer 2004-11, Vol.112 (3), p.399-406
• Main Authors: Oldford, Sharon A., Robb, J. Desmond, Watson, Peter H., Drover, Sheila
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Differentiation, B-Lymphocyte - metabolism; Antigens, Neoplasm; Biological and medical sciences; breast carcinoma; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal - immunology; Carcinoma, Ductal - metabolism; Carcinoma, Ductal - pathology; Carcinoma, Lobular - immunology; Carcinoma, Lobular - metabolism; Carcinoma, Lobular - pathology; CD3 Complex - metabolism; Cohort Studies; Female; Genes, MHC Class I - immunology; Genes, MHC Class I - physiology; Gynecology. Andrology. Obstetrics; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; HLA-DR Antigens - immunology; HLA-DR Antigens - metabolism; HLA‐DR expression; HLA‐DRB alleles; Humans; Immunoenzyme Techniques; Immunophenotyping; invariant chain; Lymphocytes, Tumor-Infiltrating - immunology; Male; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Invasiveness - pathology; Prognosis; T-Lymphocytes - immunology; Tumors; T‐cell infiltration
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20441

The biologic and prognostic significance of HLA‐DR expression and T‐cell infiltration in breast carcinoma are presently controversial. To test the hypothesis that these factors are influenced by particular HLA‐DRB alleles, 52 breast tumor samples, composed of 26 DRB1*04 and 26 non‐DRB1*04 tumors, were assessed using immunohistochemistry for expression of DR and its associated invariant chain (Ii) and for infiltrating CD3+ T cells. While DR expression by tumor cells was significantly associated with T‐cell infiltration, DRB1*04 tumors were more frequently DR+Ii+ and contained smaller CD3+ infiltrates than non‐DRB1*04 tumors. This difference was largely attributable to DRB1*07 tumors, which were typically DR−Ii−, although they contained similar numbers of T cells to DR+Ii+ tumors. Further analysis of DR+ tumors using allotype discriminating antibodies revealed that DRB1*04 alleles were always expressed, while non‐DRB1*04 alleles were inconsistently expressed. The results of this study provide the first reported evidence that DRB alleles influence DR expression and T‐cell infiltration in breast carcinoma and suggest that multiple factors contribute to DR expression. Ongoing studies aimed at elucidating the molecular and immunologic mechanisms controlling differential DR expression and implications for prognosis and outcome should further our understanding of the antitumor immune response and evasion strategies employed by tumor cells. © 2004 Wiley‐Liss, Inc.