Breast cancer immunophenotype and its relationship with haematopoiesis

Background. The applying of immunotherapeutic approaches in cancer treatment requires a deep and comprehensive understanding of the tumor biological characteristics. In this regard, the study of the tumor immunophenotype is one of the leading scientific directions. The major histocompatibility complex molecules are considered to be the promising markers of the immunotherapy effectiveness prediciton.

Aim. To research tumor immunophenotype in different molecular subtypes of breast cancer (BC).

Materials and methods. The study included 99 patients with BC. Luminal cancer – 84.8% (n=83), Erb-B2 overexpressing (HER2+) subtype – 5.0% of cases (n=5), triple-negative BC – 10.2% (n=10). Stages: T1 (51.5%), T2 (44.4%), T3 (2.0%). Lymph node metastases (N+) were present in 39.4% (n=39) of cases. Grade of malignancy: 80.8% (G2). Samples of tumor tissue and bone marrow were examined. Immunophenotyping of the tumor was carried out on cryostat sections by the method of immunofluorescense. Antibodies to HLA-I, HLA-DR, CD71 were used and were directly conjugated to fluorochromes PE, FITC, PE-Cy5. The bone marrow was examined by a morphological method using light microscopy. Statistical data processing was performed using the IBM-SPSS statistics v2.1.

Results. In 50.8% (31/61) cases of luminal BC (LBC), the HLA-I molecule is absent on the membrane or is expressed by single tumor cells. A decrease in HLA-I expression levels in the luminal subtype was combined with the absence of HLA-DR antigens, which was found in 63.1% of cases. A higher frequency of HLA-I expression is observed in the Erb-B2 overexpressing BC, the differences are insignificant. Expression of CD71 was defected in 67.8% (40/59) of the studied samples of LBC. CD71 was expressed on the surface of most tumor cells (70%) in triple-negative BC. There were no statistically significant differences between the studied molecular subtypes of BC. Analysis of the luminal subtypes revealed that CD71 expression was observed much more often in luminal B subtype: 76.5% (n=26) and 75% (n=3) versus 52.4% (n=11). HLA-I expressing luminal cancer were characterized by higher levels of erythroid precursors (polychromatophilic normoblasts 9.0±0.9 and 5.8±0.8%, p=0.0017; oxyphilic normoblasts (7.9±0.7 and 5.3±0.6%, p=0.008), an increase in the amount of erythroid germ cells (17.7±1.5 and 11.6±1.5%, р=0.009) and an increased content of myelokaryocytes (93.1±17.1 thousand/µl versus 57.3±9.0 thousand/µl, p=0.083).

Conclusion. In LBC a decrease in the expression levels of HLA-I class molecules was noted in combination with the absence of HLA-DR antigens on the membrane of tumor cells, which was observed in more than half of the analyzed samples. The frequency of expression in triple-negative cancer is higher than in the luminal subtype. There were no statistically significant differences between molecular subtypes by the level of expression of HLA-I and II class molecules. Transferrin receptor expression has been reported in most cases of triple-negative BC subtype. The interconnection between the expression of HLA-I histocompatibility molecules and hematopoetic parameters in LBC has been established.