Factors of the immune microenvironment and the state of the extracellular matrix in vulvar ­cancer

Background. The progression of malignant tumors, including vulvar cancer, largely depends on the state of the extracellular matrix and immune microenvironment of the tumor, the study of which is an urgent problem of oncology to identify the most prognostically significant of them.

Aim. To evaluate the expression of extracellular matrix and local immunity factors, as well as their relationships in vulvar cancer with different prevalence.

Material and methods. A retrospective study on vulvar tumors in 56 patients with stage I (n=20), stage II (n=26) and relapses (n=10) was performed. The expression of markers of the extracellular matrix (matrix metalloproteinases MMP-2 and MMP-9, tissue inhibitor of metalloproteinase-2 TIMP-2) and local immunity (FOXP3, CD68, CD206) was determined by immunohistochemical method. Statistical processing was performed using the Mann–Whitney U-test and multiple correlation analysis with the calculation of paired and partial R coefficients.

Results. The depth of invasion proved to be more informative for detecting multidirectional differences in the expression of MMP-2 and TIMP-2 than the stage. Infiltration by CD68+-macrophages in the stroma increased in parallel with the stage and did not differ at different depths of invasion; infiltration by macrophages M2 (CD206+) increased at stage II compared with stage I (Me 13 and 5, respectively, p=0.03). Differences were noted only in the stroma of tumors, as well as an increase in T-regs (FOXP3) with an increase in the depth of invasion (Me 25 and 8, respectively, p=0.0359). As the prevalence of the tumor developed, the number of correlation relationships between the parameters of local immunity of the parenchyma and tumor stroma increased: 2 statistically significant correlations that do not depend on covariates, 7 that depend on the stage, and 6 that depend on the depth of invasion, were found. Correlations of factors of the immune microenvironment with the extracellular matrix weakened.

Conclusion. The levels of MMP-2, TIMP-2, CD68+, CD206+, FOXP3 reflect the progression of vulvar cancer and can be used to predict the course of the disease; infiltration of tumors by macrophages, T-regs characterizes the stage of the primary tumor rather than recurrence.