Evaluation of the Relationship of PDL1 Expression with Lymph Node Metastasis and Prognosis in Cases Diagnosed with Classic Type Papillary Carcinoma of the Thyroid

Project no. 27395 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

Papillary Thyroid Carcinoma (PTC) is the most common thyroid malignancy of follicular cell origin in both the adult and pediatric population. In addition to typical treatment protocols in thyroid cancer, targeted therapy; it has been the focus of studies for years for radioiodine-resistant differentiated thyroid carcinomas. The positive results obtained in melanomas have led to the testing of immunotherapy in other solid tumors and successful results. The main goal of immunotherapy is to restore this ability to immune cells whose ability to recognize tumors is inhibited by various mechanisms. Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are the most powerful known immune checkpoint molecules and have revitalized the management of malignancies due to the increase in knowledge on this subject over time. Currently, the PD-1/PD-L1 checkpoint pathway is considered the most important target in the development of immunotherapy. It is thought that the patient population that will benefit from treatments that will block PD-1 and PD-L1 can be determined by evaluating PD-1 and PD-L1 expression in tumours. Studies have shown that PD-L1 can also be expressed in thyroid cancers and reported its predictive and therapeutic value. However, much more work is needed to expand the role of PD-L1 immunohistochemistry regarding the underlying molecular subgroups of PTCs and the response to checkpoint inhibitor therapy in radioactive iodine-resistant PTCs. Tumor-infiltrated immune cells represent mononuclear cells in the tumor and tumor microenvironment. Although it has been shown to be a good prognostic marker in most malignancies, there are not enough studies in this regard in thyroid cancers. 100 cases (with or without lymph node metastasis) who were diagnosed with PTC, Classic Type at the Pathology Department of Ege University Faculty of Medicine between 2000 and 2010 were included in our study. We compared the rate of PD-L1 in tumors and tumour infiltrating immune cells with clincopathological data by categorizing them according to different cutoff values frequently used in the literature. We divided the cases into three groups; negative, <%1 and ≥%1 PD-L1 staining, and all cases were evaluated according to age, gender, tumor size, capsule presence, capsule invasion status, infiltrative pattern, multicentricity status, surrounding soft tissue spread, lymph node metastasis status. We compared the status and PD-L1 staining. We did not detect any statistically significant differences between groups and clinicopathological parameters in univariate analyses. In multivariate analyzes (logistic regression analysis), we found female gender and PD-L1 immunohistochemical expression to be statistically significant. When we compared PD-L1 staining with similar clinicopathological data of all cases by dividing them into three groups as “negative”, “≥%1 and <%5” and “%≥5” PD-L1 staining, we did not detect a statistically significant difference. When we divided the cases into two groups as PD-L1 negative and positive cases in the tumor, we found a significant relationship between tumor size and PD-L1 expression in multivariate analyses (We determined that tumor size larger than 2 cm increased PD-L1 staining by 5.26 times). Additionally, we divided the stained cases into three groups according to their staining intensity; mild (1+), medium (2+) and strong (3+) staining and determined the PD-L1 staining intensities. We did not detect a statistically significant relationship when we compared it with clinicopathological data. In our study, the relationship between PD-L1 and clinicopathological data in different categories was compared. Consistent with the literature, no significant relationship was found with age, infiltrative pattern, multicentricity status, surrounding soft tissue spread, lymph node metastasis and pT. While there are literature data supporting the female gender and tumor size data, which were found to be significant in our study, there are also studies that did not find these parameters statistically significant with PD-L1. More and comprehensive studies are needed to determine the effectiveness of treatments that will block PD-1 and PD-L1 in thyroid cancer and PTCs and to determine the patient population that will benefit from these treatments.

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