title: Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis.
abstract: Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.
authors.affiliation: Department of Biochemistry, Hospital Costa del Sol, Marbella, Spain.
authors.forename: Maximino
authors.initials: M
authors.lastname: Redondo
authors.forename: Julian
authors.initials: J
authors.lastname: García
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villar
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodrigo
authors.forename: Emilio
authors.initials: E
authors.lastname: Perea-Milla
authors.forename: Alfonso
authors.initials: A
authors.lastname: Serrano
authors.forename: Miguel
authors.initials: M
authors.lastname: Morell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D005260:Female; D019254:Genes, bcl-2 / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000276:immunology; D011230:Precancerous Conditions / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001613:beta 2-Microglobulin / Q000096:biosynthesis
chemical_list: C494826:BAX protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D001613:beta 2-Microglobulin