HLA-DR antigens on differentiating human mammary gland epithelium and breast tumours

Abstract

Summary The staining pattern of a monoclonal antibody directed to the monomorphic determinant of HLA-DR antigens was examined on sections of human mammary gland tissues at various stages of differentiation as well as on 50 benign and 72 malignant breast lesions. Normal resting breast epithelium lacked HLA-DR, whereas late-pregnant and lactating epithelia expressed high levels of HLA-DR antigens, followed by a decline in the post-weaning regression period. Most benign breast lesions revealed heterogeneous staining ranging from very few up to 20-25% positive epithelial cells. Greater variability was observed among carcinomas, where a small group (-7%) of cases showing 40-95% positive tumour cells was found, in addition to negative tumours and those with the minority of HLA-DR expressing carcinoma cells. The density of the leukocytic infiltrate was higher in carcinomas than in either normal breast tissue or benign lesions, the HLA-DR phenotype of the mononuclear infiltrating cells lacking any obvious correlation with the HLA-DR status of the epithelial component. Immunoblotting analyses of whole-tissue lysates separated by SDS-PAGE confirmed the immunohistochemical data and demonstrated the reactivity with only one protein band predicted for HLA-DR a-chain. The combination of immunohistochemistry and autoradiography on sections of human reduction mammoplasty organoids cultured in collagen gels and labelled with tritiated thymidine revealed a lack of HLA-DR expression on proliferating breast epithelial cells suggesting factors other than cell kinetics must be responsible for induction of HLA-DR antigens seen in pregnant and lactating breast epithelium and some tumours.

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

“…Discordant findings regarding the levels of HLA-DR expression were reported in breast cancer (Natali et al, 1983;Bernard et al, 1984;Hurlimann and Saraga, 1985;Bartek et al, 1987;Walker, 1987, 1988;Koretz et al, 1989;Moller et al, 1989;Brunner et al, 1991;Concha et al, 1991;Lucin et al, 1994). Furthermore, in breast cancer, the extent of HLA-DR expression appears to be related to tumor grade.…”

“…Furthermore, in breast cancer, the extent of HLA-DR expression appears to be related to tumor grade. In fact, two studies reported that none of the breast carcinomas that were negative or only focally positive for HLA-DR expression were well differentiated (Zuk and Walker, 1988;Brunner et al, 1991); in addition, high levels of HLA-DR antigens expression were detected on primary medullary breast carcinoma which is usually associated with a relatively favorable prognosis (Natali et al, 1983;Bartek et al, 1987;Yazawa et al, 1993;Feinmesser et al, 2000;Lazzaro et al, 2001). In spite of these evidences, a number of studies failed to support a prognostic relevance of HLA-DR antigens in breast cancer (Perez et al, 1986;Wintzer et al, 1990;Lucin et al, 1994).…”

Inflammatory infiltrate in invasive lobular and ductal carcinoma of the breast

“…Normal breast epithelium shows no expression of HLA-DR (Bartek et al, 1987;Lucin et al, 1994), except during late pregnancy and lactation (Bartek et al, 1987 …”

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

“…Unlike HLA class I, HLA class II molecules are not normally present on resting epithelial cells, although they are detected de novo in the lactating breast and in a subset of breast carcinomas. 6 They can also be induced in vitro on many cell types, including breast cancer cell lines, by interferon-␥ (IFN-␥) 7,8 and other immunomodulators, 9,10 suggesting that in situ expression on carcinoma cells may be regulated by cytokines and/or hormones. Antigen presentation by HLA class II ϩ breast cancer cells, which lack costimulatory molecules typically found on professional antigen presenting cells (APCs), could potentially induce T-cell anergy.…”