Immunohistochemical investigations on the expression of programmed cell death ligand 1, human leukocyte antigens G and E, and granzyme B in intraoral mucoepidermoid carcinoma

Abstract Objective To identify the expression of nonclassical human leukocyte antigen G and E (HLA-G and -E), programmed cell death ligand-1 (PD-L1) and granzyme B (GB) in intraoral mucoepidermoid carcinomas (MECs), and to assess whether such expressions are related to metastasis, survival, staging, tumor grade and number of GB-positive cells. Design For this cross-sectional study, samples of MEC (n = 30) were selected and classified as low-grade (LG), intermediate-grade (IG) or high-grade (HG), according to the WHO grading system. HLA-G, -E and PD-L1 were identified by immunohistochemistry and quantified as the proportion of positive neoplastic cells. The density of GB+ cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level. Results Expressions of HLA-G, -E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. The quantitative analysis of the total percentage of positive neoplastic cells showed overexpression of this set of proteins in all MEC samples. The expression of these proteins and histological grading were positively correlated [HLA-G (LG = 79% positive cells, IG = 96%, HG = 99%; p  = 0.0004), HLA-E (LG = 70%, IG = 96%, HG = 99%; p   0.0001) and PD-L1 (LG = 34%, IG = 79%, HG = 80%; p  = 0.01)]. No relationship was observed between the immunosuppressive proteins and other clinicopathological parameters. Low GB density was found in all MEC samples. Conclusions The augmented expression of HLA-G, -E and PD-L1 in the intraoral MEC might suggest a role of these molecules in the scape of neoplastic cells from immunosurveillance.