Total loss of MHC class I is an independent indicator of good prognosis in breast cancer
Madjd, Zahra and Spendlove, Ian and Pinder, Sarah E. and Ellis, Ian O. and Durrant, Lindy G. (2005) Total loss of MHC class I is an independent indicator of good prognosis in breast cancer. International Journal of Cancer, 117 (2). pp. 248-255. ISSN 0020-7136
Official URL: http://onlinelibrary.wiley.com/doi/10.1002/ijc.21163/abstract;jsessionid=0F2D2BA7158A645CEAA0FEC990F1DD0E.f02t04
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-β2m-antibody staining was observed in 39% (167 of 424) of tumours, with only 3% of the β2m-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-β2m 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 β2m = 0.018).
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