Immunohistochemical Expression of CD16, CD56, HLA-E, and HLA-C in Endometrial Carcinoma: Implications for NK Cell–Mediated Immune Evasion

Endometrial carcinoma is a common gynecological malignancy characterized by an altered and immunosuppressive tumor microenvironment. Natural killer (NK) cells play an important role in anti-tumor immunity. However, their activity may be impaired through inhibitory signaling pathways that facilitate immune evasion. This study aimed to evaluate the immunohistochemical expression of NK cell markers (CD16 and CD56) and inhibitory ligands (HLA-E and HLA-C) in EC and to investigate their associations with immune evasion, age, and clinicopathological parameters. A case-control study was conducted on 44 endometrial tissue specimens, including 22 primary EC cases and 22 nonmalignant controls collected from hospitals in Basrah, Iraq. Immunohistochemistry (IHC) was used to assess marker expression, and statistical analyses were performed using Chi-square, Fisher’s exact, and Spearman correlation tests. CD16 and CD56 expression was significantly higher in EC tissues compared with controls (50.0% vs. 0.0%, p < 0.001; 68.2% vs. 9.1%, p < 0.001, respectively). Although HLA-E and HLA-C expression was elevated in EC tissues, the differences were not statistically significant. A strong positive correlation was observed between HLA-E and HLA-C expression (r = 0.68, p < 0.001). Moderate positive correlations were also identified between NK-related markers and inhibitory ligands, particularly between CD16 and HLA-E (r = 0.37, p = 0.013). No significant associations were found between marker expression and clinicopathological parameters. However, HLA-C expression showed a significant negative correlation with age groups (r = −0.426, p = 0.048). These findings support the potential role of HLA-E/NKG2A and HLA-C/KIR pathways in NK cell–mediated immune evasion in EC.