Features of the Lymphoid Microenvironment in Invasive Ductal Breast Cancer
Authors:   Danylo Halytsky Lviv National Medical University, Department of Pathological Anatomy and Forensic Medicine. 69, Pekarska Str., Lviv 79010, Ukraine, Volos L. I. , Dudash A. P. 
Published: December 2021

The purpose of the study was to assess the distribution of tumor-infiltrating T-, B-lymphocytes and natural killer cells in various molecular subtypes of invasive ductal breast cancer and to establish their relationship with the degree of tumor differentiation. Materials and methods. The basis of the scientific work was a complex morphological, including immunohistochemical study of 193 cases of invasive ductal breast cancer. General histological processing of the samples was carried out in accordance with the standard technique. Immunohistochemical studies for CD3, CD20, CD56, ER, PR, c-erbB2, Ki-67 were performed according to the manufacturer's protocol with the control of samples. The grade of malignancy was determined according to the modified scheme of P. Scarff, H. Bloom and W. Richardson. The presence, localization, and expression intensity of diagnostic and prognostic biomarkers CD3, CD20, and CD56-positive cells (T-, B-, and natural killer cells, respectively) were determined using the new bioimage analysis software QuPath. Results and discussion. The differences obtained in our study varied depending on the subpopulations of immune cells and their location in the tumor tissue. The density of T and B lymphocytes was higher within the tumor and in the invasive margin in the non-luminal phenotypes compared to the luminal A and B phenotypes. Compared to the density of T-lymphocytes, the B-cell infiltrate was significantly (p <0.01) less pronounced in tumors of both luminal and non-luminal phenotypes. The lowest density of natural killer cells among tumor-infiltrating lymphocytes was found within the tumor of luminal subtypes. The percentage of infiltrates of T and B cells both within the tumor focus and in the invasive margin, as well as natural killer cells in the invasive margin, was significantly lower with G1 and G2 than with the degree of differentiation G3 (p <0.01). As for intratumoral natural killer cells, differences were found only between the degree of differentiation of G2 and G3, and the differences between G1 and G2 were not statistically significant (p> 0.05). Qualitative and quantitative assessment of the intensity of expression of T-, B- and natural killer cells also demonstrated a different degree of expression of lymphocytes, depending on the molecular subtype and location of the infiltrate. The luminal subtype A was characterized by a significant predominance of mild expression (2+) CD3 both within the tumor and in the invasive margin of the tumor (p <0.05), while in the luminal B and Her2 + phenotypes, the intensity of CD3 expression prevailed at the 1+ level. Triple negative tumors were characterized by strong expression of (3+) CD3 within the tumor and in the invasive margin of the tumor in all cases studied. Conclusion. Thus, tumor-infiltrating lymphocytes in different molecular subtypes of invasive ductal breast cancer can be considered a prognostic biomarker. Our results indicate a relationship between lymphoid infiltrate and the degree of differentiation in invasive ductal breast cancer, especially in less favorable molecular subtypes