Expression of monomorphic HLA-determinants, transferrin receptor 1 (TfR1) in molecular subtypes of breast cancer
Authors: Chulkova S. V. , Sholokhova E. N. , Poddubnaya I. V. , Stylidi I. S. , Tupitsyn N. N. 
Published: December 2022

Background. Immunotropic drugs are widely used in the modern strategy of cancer treatment. Importance is given to immunological markers of the tumor, which determine the prognosis of the disease, the effectiveness of treatment. Therefore, the study of their expression is one of the leading scientific directions. Of particular interest is the study of monomorphic HLA determinants, transferrin receptor 1 (TfR1), depending on its biological subtype of breast cancer.

Aim. To evaluate the frequency of expression of HLA class I, II, TfR1 molecules by breast cancer cells and determine their relationship with the molecular biological subtype of the tumor.

Materials and methods. This study included 120 patients with breast cancer who received treatment at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. Tumor stages II and III prevailed: 56.7 % and 33.4 %, respectively. A moderate degree of differentiation (G2) was more often noted. The luminal subtype was 58.3 % (n = 70), non-luminal – in 41.7 % (n = 50). 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 frequency of expression of HLA class I and II molecules were studied depending on the clinical and morphological characteristics of breast cancer. The frequency of expression of HLA class I, HLA-DR, TfR1, molecules, toumor infiltration of СD45+, CD38+, depending on the molecular subtype of breast cancer was studied.

Results. It was found that the frequency of expression of monomorphic determinants of the HLA class I in luminal and non-luminal subtypes of breast cancer was comparable; HLA-DR was expressed significantly more often in the luminal subtype of breast cancer: 37.3 % and 18.0 %, respectively, p = 0.022. The frequency of TfR1 expression was significantly higher in the luminal subtype of cancer compared to non-luminal, p = 0.014. Predominantly monomorphic type of reaction was observed: in 76.5 % (n = 39) of cases. The mosaic type of the TfR1 reaction was noted in 7.8 % of the samples. TfR1 monomorphic expression was detected in 50.0 % (n = 30) of cases in non-luminal cancer, the mosaic expression – in 20.0 % (n = 12) of cases. A pronounced degree of lymphoid infiltration, in particular plasmacytic, was established in non-luminal subtype of breast cancer: 70.7 % (n = 29) and 35.0 % (n = 14), respectively, p = 0.001. An association was noted between the expression of HLA I class molecules and the severity of general leukocyte infiltration, p = 0.007.

Conclusion. The frequency of expression of HLA class I monomorphic determinants did not differ in molecular subtypes of breast cancer. The expression of the HLA class II molecule was significantly more frequently observed in the luminal subtype of breast cancer. The expression of HLA class I monomorphic determinants is associated with the degree of lymphoid infiltration of the tumor. In the non-luminal subtype, plasmacytic infiltration is more pronounced. The expression of transferrin receptors is significantly more pronounced in the luminal subtype.