title: Total loss of MHC class I is an independent indicator of good prognosis in breast cancer.
abstract: Tumours can be recognised by CTL and NK cells. CTL recognition depends on expression of MHC Class I loaded with peptides from tumour antigens. In contrast, loss of MHC Class I results in NK activation. In our study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC Class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty-seven percent (206 of 439) of breast carcinomas were considered negative for HLA Class I heavy chain (HC10), whereas lack of anti-beta2m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the beta2m-negative tumours expressing detectable HLA Class I heavy chain. Correlation with patient outcome showed direct relationship between patient survival and HLA-negative phenotype (log rank = 0.004). A positive relationship was found between the intensity of expression of MHC Class I light and heavy chains expression and histological grade of invasive tumour (p < 0.001) and Nottingham Prognostic Index (p < 0.001). To investigate whether HLA Class I heavy and light chains expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-beta2m staining, was carried out. In our analysis, lymph node stage (p < 0.001), tumour grade (p = 0.005) and intensity of MHC Class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (p-values HC10 = 0.047 and beta2m = 0.018).
authors.affiliation: Cancer Research UK Academic Unit of Clinical Oncology, Nottingham City Hospital, United Kingdom.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Madjd
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000172:deficiency
chemical_list: D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin