The relationship of pd-l1 and braf v600e staining scores with prognostic factors in papillary thyroid cancers

Thyroid carcinoma is the most common of all endocrine tumors. Thyroid cancer incidence and mortality rates are gradually increasing. Papillary thyroid carcinoma (PTC) constitutes the largest portion of thyroid carcinomas with good prognosis. However, about 10% of all thyroid cancers have a poor prognosis. Therefore, it is important to identify clinicopathological factors that facilitate better estimation of patient prognosis and planning the appropriate treatment. In the studies conducted for this purpose, it is suggested that determining the PD-L1 staining rates and BRAF V600E mutation status as well as the standard criteria used to determine the prognosis in PTCs may be important alternatives. Also, the effect of concurrent Hashimoto thyroiditis (HT) on tumor microenvironment and PTC progression is not well understood. It is known that immune checkpoint pathways, including the programmed death receptor-1 / programmed death ligand-1 (PD-1 / PD-L1) signaling pathway, play an important role in mediating and controlling self-tolerance. This mechanism can sometimes be manipulated by cancer cells to evade the immune system. Recently, there is an increased focus on the immune checkpoint protein PD-1 and ligand PD-L1, due to the discovery that blocking the PD-1 / PD-L1 pathway with monoclonal antibodies has striking clinical consequences in many different malignancies. PD-1 is expressed on activated T cells, especially high expression by tumor-infiltrating T lymphocytes (TILs). In recent years, some molecular pathways that are thought to be responsible for the development and invasiveness of PTC have been elucidated. In this context, the most widely accepted pathway has been the RET-RAS-RAF-MEK-ERK (mitogen-activating protein kinase) pathway, in which the BRAF V600E mutation plays a prominent role. The purpose of this study is to answer the following questions: (1) Which clinicopathological factors affect PD-L1 expression in PTCs? (2) Which clinicopathological data affect BRAF V600E expression in PTCs? (3) Is there a relationship between BRAFV600E expression and increased PD-L1 expression, one of the immune mechanisms that may help explain poor prognostic outcomes, in PTC patients with high BRAFV600E staining scores? (4) Is there a difference between PD-L1 expression and PTCs that develop and do not develop in the HT background? In this thesis study, patients who underwent total thyroidectomy between June 2013 and December 2019 in the archive of Başkent University Faculty of Medicine Ankara Hospital Department of Pathology and diagnosed with PTC with a diameter of 1 cm or more were included. Of the 81 PTC cases detected, 71 were reported as classical variant, 4 as follicular variant, 4 as oncocytic variant and 2 as diffuse sclerosing variant. 42 of these cases included in the study were accompanied by HT. Hematoxylin & Eosin sections of the cases were reviewed and clinicopathological parameters were evaluated. PD-L1 and BRAF V60E antibodies were studied in all cases by immunohistochemistry. Statistically significant, while all patients under the age of 55 are TNM stage I, all cases with TNM stage II are older than 55 years and the proportion of female patients diagnosed with PTC is approximately 4 times higher than male patients. A statistically significant level of multifocality was detected in cases with lymph node metastasis and lymphovascular invasion. It was found that lymphovascular invasion with minimal extrathyroidal spread was corole. A statistically significant minimal extrathyroidal spread was observed in cases with positive surgical margins. The number of female patients with HT was found to be 7 times higher than male patients. A statistically significant difference was observed between the PD-L1 expression rate according to the tumor variants. Comparison of PD-L1 expression rates according to other clinicopathological parameters such as TNM stage, tumor size, multifocality, pN, pT, extrathyroidal invasion, surgical margin and lymphovascular invasion was not found to be significantly different. A statistically significant difference was observed between the PD-L1 expression rate in the presence of HT, and it was found that the PDL-1 expression rate was higher in PTC patients with HT. BRAF V600E staining scores were found to be higher than pT1a in the pT1b stage. Comparison of BRAF V600E staining scores according to other clinicopathological parameters such as TNM stage, tumor size, multifocality, pN, tumor variant, extrathyroidal invasion and lymphovascular invasion was not found to be significantly different. BRAF V600E staining scores were not found to be statistically different in PTC patients with and without HT. As a result, although PD-L1 is not yet used as an accepted prognostic marker for PTC, it has been suggested that PD-L1 can be used as a marker in terms of determining the prognosis of PTCs developing on the basis of HT and directing the treatment. Since BRAF V600E staining scores in pT1b stage were higher than pT1a, it was thought that BRAF V600E staining scores might be higher in advanced pT stage and could be used to predict advanced stage disease. In addition, the higher BRAF V600E staining scores in cases with positive surgical margins suggested that BRAF V600E positivity might indirectly predict recurrent disease. The correlation between PD-L1 staining rates and BRAF V600E score in our study, due to the fact that the presence of BRAF V600E mutation is associated with poor prognostic parameters in the literature, suggested that PD-L1 may be useful in predicting poor prognosis. However, the current findings should be supported by studies with more patients.