Human Leukocyte Antigen Class I Expression and Natural Killer Cell Infiltration and Its Correlation with Prognostic Features in Luminal Breast Cancers

Maria Vernet-Tomas,1,2 Ivonne Vazquez,1,3 Francesc Olivares,3 David Lopez,3 Jose Yelamos,2,4 Laura Comerma1– 3 1Breast Diseases Unit, Hospital Del Mar, Barcelona, Spain; 2Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; 3Department of Pathology; Hospital del Mar, Barcelona, Spain; 4Laboratory of Immunology, Department of Pathology; Hospital Del Mar, Barcelona, SpainCorrespondence: Maria Vernet-Tomas, Breast Diseases Unit, Hospital del Mar, Passeig Marítim de la Barceloneta 25- 29, Barcelona, 08003, Spain, Tel +342483132, Email mvernet@hmar.catPurpose: The aim of this study was to determine whether low HLA-I expression and NK cells infiltration are related to prognostic features in breast cancer, as observed in cancers in other locations and non-hormone dependent breast cancers. Particularly, we explored their relation to infiltrated axillary lymph nodes (ALNs), with the aim of finding new predictors helping to decide the extent of axillary surgery.Patients and Methods: We conducted a retrospective correlational analysis of 35 breast cancers from 35 breast cancer patients showing axillary infiltration at diagnosis and with upfront surgery. HLA-I H-score and the number of NK cells x 50 high power fields (HPF) in the biopsy specimen were correlated with pathological variables of the surgical specimen: number of infiltrated ALNs, tumor size, histological type, the presence of ductal carcinoma in situ, focality, histological grade, necrosis, lymphovascular and perineural invasion, Her2Neu status, and the percentages of tumor-infiltrating lymphocytes (TILs), estrogen receptor, progesterone receptor, ki67, and p53.Results: All tumors showed hormone receptor expression and three of them Her2Neu positivity. A positive correlation (p=0.001**) was found between HLA-I H-score and TILs and Ki67 expression. HLA H-score increased with histological grade and was higher in unifocal than in multifocal disease (p=0.044 and p=0.011, respectively). No other correlations were found.Conclusion: High HLA-I H-score values correlated with features of poor prognosis in this cohort of luminal breast tumors, but not with infiltrated ALNs. This finding highlights the differences between luminal breast cancer, and cancers in other locations and non-hormone dependent breast cancers, in which low HLA-I expression tends to be associated with poor prognostic features.Keywords: luminal breast cancer, HLA-I, natural killer cells, prognostic features, axillary lymph nodes