Clinicopathological significance of programmed deathligand -1 (PD-l1) and lymphocyte activation gene -3 (LAG-3)expressions in cutanosus squamous cell carcinoma

Cutaneous Squamous Cell Carcinomas (cSCC) are the second most common non-melanoma skin cancer. Although it can be diagnosed at an early stage, it is the first cause of death from non-melanoma skin cancers. Most cases are easily treated with surgical excision, advanced-stage SCC cases with high-risk criteria relapse, metastasize, and cause of death and their treatment is limited. However, in recent years, immunotherapy and checkpoint inhibition therapy have shown promise for the treatment of SCC. The aim of this study was to examine the immunohistochemical expressions of PD-L1 and LAG-3 in SCC cases and to evaluate their relationship with known prognostic factors for SCC such as tumor localization, TNM stage, tumor invasion depth, perineural invasion and amount of tumor infiltrating lymphocytes. Thus, we aim to use the expression of PD-L1 and LAG-3 by tumor and immune cells as a prognostic indicator and potential targets for treatment, especially in advanced stage SCC whose treatment is currently limited. The study included 74 cases (ear in 25 cases, face in 25 cases and extremities in 24 cases) diagnosed with squamous cell carcinoma of the skin between 2019-2020 at Adnan Menderes University Faculty of Medicine, Department of Pathology. Age and gender distribution, localization, tumor size, TNM stage, depth of invasion, LVI, PNI status and amount of TIL were analyzed. PD-L1 and LAG-3 were used for immunohistochemistry. As a result of the analysis, PD-L1 expression was positive in almost all of the cases (91.5%), while LAG-3 expression was found to be positive in the majority of the cases (62.2%). The relationship between PD-L1 expression, tumor localization and PNI status was statistically significant. In ear localized cases with poor prognosis, PD-L1 expression was more positive than other localizations (p<0.001) PD-L1 expression; It was detected more in tumors with pni than those without pni (p=0,002). The relationship between LAG-3 expression and male gender and tumor localization was statistically significant. LAG-3 expression was more positive in cases located in the ear compared to other localizations (p<0.001). In addition, a significant correlation was found between PD-L1 and LAG-3 expressions (p=0.002). PD-L1 expression was also positive in all cases with positive LAG-3 expression. The findings support PD-1/PD-L1-targeted therapies that have recently entered clinical use in the treatment of SCCs. however, the fact that PD-L1 and LAG-3 are co-expressed in the majority of our cases is promising, especially in the group of patients who do not respond to treatment. In future studies, it is thought that in large series with more cases, immunohistochemical antibody clones will become suitable for clinical use if the protocols and interpretations used become standardized.