Comparison of CTLA-4 and PD1 in oral leukoplakia and oral squamous cell carcinoma: an immunohistochemical analysis.

This study discusses immune checkpoint proteins Cytotoxic T-Lymphocyte Associated Protein 4(CTLA-4) and Programmed Cell Death Protein 1 (PD1), which have significant implications in the immune evasion of tumors. When it comes to oral squamous cell carcinoma (OSCC) and other potentially malignant disorders, their appearance is not completely understood. To compare and evaluate the immunohistochemical patterns of CTLA-4 and PD1 in oral leukoplakia and OSCC and compare the patterns with clinicopathological parameters. Formalin-fixed and paraffin-embedded tissues from 30 cases of OSCC and 30 cases of oral leukoplakia were stained using immunohistochemistry. For scoring, a semi- qualitative scale with arrange of 0–3 + was used. OSCC exhibited significantly higher levels of CTLA-4 and PD1 expression than oral leukoplakia (p = 0.003 and p < 0.001, respectively). In leukoplakia and OSCC, the mean expression scores for CTLA-4 and PD1 were 1.17 ± 0.95 vs. 1.97 ± 0.96 and 1.07 ± 1.02 vs. 2.07 ± 0.91, respectively. CTLA-4 expression and PD1 showed a significantly significant positive association (ρ = 0.612, p < 0.001). Both were found to be related to the severity of the disease and the differentiation of the tumor. Combinations of markers provided the best diagnostic performance (AUC = 0.842, sensitivity = 83.3%, specificity = 76.7%). Oral carcinogenesis is characterized by increased expression of CTLA-4 and PD1 and can be useful biomarkers to identify the differences between malignant and premalignant lesions of the mouth. Their simultaneous expression implies possible therapeutic sites to be addressed through immune checkpoint inhibition in oral cancer.