Análise imunoistoquímica das subpopulações M1 e M2 de macrófagos associados a tumores (MATs) em carcinomas de células escamosas de lábio inferior

Abstract

By the direct action of ultraviolet and excluding skin changes, the lower lip is the structure most affected by potentially malignant and malignant lesions of epithelial origin. One factor that may step in the prognosis of squamous cell carcinoma of the lower lip (SCCLL) consists of the components of the tumor microenvironment. The tumor-associated macrophages (TAMs) are part of this cell population and are divided according to their state of polarization: M1 subtype (classical activation), exerts anti tumor properties through the destruction of neoplastic cells and subtype M2 (alternative

activation), which have anti-inflammatory activity and promotes neoplastic cells escape

immune

surveillance. Numerous studies have demonstrated the involvement of TAMs and poorer prognosis in several malignancies, however its relationship with SCCLL is not yet known. The present study aimed to analyze, through immunohistochemistry, the presence of M1 and M2 subpopulations of TAMs in a series of cases of SCCLL and verify a possible involvement of these cell subsets in the development of lymph node metastasis. Histological sections stained with hematoxylin and eosin, obtained from 30 cases of SCCLL and divided into two groups (15 cases with lymph node metastasis and 15 cases without lymph node metastasis), were evaluated under light microscopy where it determined the histopathological grading of malignancy. The material was subjected to double staining technique for the monoclonal antibodies anti-CD68, anti-CD163 and anti-HLA-DR. Obtained distinction between TAMs M1 (CD68/HLA-DR) and TAMs M2 (CD68/CD163). Then the immunostained cells were counted in 10 fields higher positive, establishing the average of M1 and M2 TAMs in each case. The data obtained from the measurements of TAMs M1 and M2 were subjected to the KolmogorovSmirnov test, which revealed the absence of normal distribution. Possible differences in

the

amounts of these cell types in relation to clinicopathological parameters were evaluated using the nonparametric test Mann-Whitney. Probable correlation in the amounts of TAMs M1 and M2 was verified by Spearman test. The analysis of tumor invasion front revealed the presence of the two cell subsets (TAMs M1 and M2). The TAMs M1 presented significant association in the largest lesions (T2-T4) (p = 0.049). With respect to the absence / presence of lymph node metastasis, clinical stage and histological grading of malignancy, there was no statistically significant difference. However, visualized weak positive correlation was statistically significant between the TAMs M1 and M2 (r = 0.385, p = 0.036). Thus it is concluded that the TMAs are not involved in tumor invasion SCCLL. However they are important for understanding the biological behavior of the disease. Furthermore, this study encourages the development of new research on the various components of the tumor microenvironment in order to signal paths that seek to enhance and individualize treatments for cancer, getting better quality of life for patients suffering from this disease.