HLA-monomorphic determinants of the primary tumor in breast cancer patients

Abstract

Background. Molecules of the major histocompatibility complex in cancer are currently being widely studied, and their clinical significance is still the subject of controversy. It is reported that they might have an important predictive value in the effectiveness of immunotherapy. The study of the expression HLA molecules status in breast cancer provides a deeper understanding of the biological properties of the tumor, in particular to identify the features of its immunological phenotype, which may further influence on breast cancer therapy.Aim. To evaluate the frequency of HLA-immunophenotypes in breast cancer and their relationship with the clinical and morphological features of the primary tumor.Materials and methods. This study included 82 patients with breast cancer who received treatment at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. Immunophenotyping of the primary tumor was performed by immunofluorescence on cryostat sections. The reaction was evaluated using a ZEISS Axioscope 5 luminescent microscope (Zeiss AG, Germany). The study was dominated by patients with stage IIB 54 %, stage IIA was detected in 5 % of cases, IIIA – in 12 % of cases, IIIB – in 21 % of cases, IIIC – 8 %. Infiltrative ductal breast cancer was diagnosed in 67 % of patients (n = 55), infiltrative-lobular – in 22 % of cases (n = 18), other types – in 11 % (n = 9). The frequency of immunophenotypes was studied depending on the clinical and morphological characteristics of breast cancer.Results. It was found that in the group as a whole, the HLA-binegative immunophenotype of breast cancer was predominant. It dominated at stage T4 compared to the HLA-I+/HLA-DR+ phenotype (100 and 0 %), p = 0.042. At the same time, it should be noted that in T4 primary tumor the HLA-I+/HLA-DR– immunophenotype was also observed. The relationship this immunophenotype was noted with the stage: frequency at stage IIIA was higher than the HLA-I+/HLA-DR+ phenotype, 60 and 40 %, p = 0.01. Both HLA-DR-negative immunophenotypes were characterized by a high incidence of lymph node involvement and the absence of estrogen receptor expression. 80 % of receptor-negative tumors were noted in HLA-binegative immunophenotype compared to phenotype HLA-I+/HLA-DR+, p = 0.022; the similar data were obtained for the HLA-I+/HLA-DR– immunophenotype (p = 0.037).Conclusion. HLA immunophenotypes analysis of breast cancer revealed the HLA-binegative immunophenotype of breast cancer was predominant. The second most common immunophenotype was the absence of expression of HLA-DR molecules. The association of HLA-immunophenotypes with the stage of the tumor process, the size of the primary tumor, and the expression status of estrogen receptors was revealed.