ROLE OF MCL-1 , PDL-1 AND KI-67 IN TUMOR PROGRESSION, RECURRENCE AND OUTCOMES IN ADVANCED THYROID CANCER.

Abstract

Context: The prognostic role of molecular markers in differentiated thyroid cancer (DTC) is a matter of ongoing discussion. Mcl-1, PD-L1 and Ki-67 are involved in several carcinogenic mechanisms enrolled in thyroid cancer. Mcl-1 is overexpressed in papillary thyroid cancers (PTC) and Ki-67 was related to poor prognosis in PTC. However, a correlation between Mcl-1 and Ki-67 concurrent overexpression's and outcomes in advanced thyroid cancer has not been extensive clarify. Objectives: This study aimed to investigate the clinical utility of the Ki-67, PD-L1 and Mcl-1 immunochemical overexpression's' in thyroid tumors and to investigate the prognostic significance in a large cohort of intermediate and high-risk DTC patients in long-term follow up. Design and Setting: Retrospective observational study of a large series of DTC cases with a long follow-up was investigated for PD-L1, Ki-67 and Mcl-1 expressions. The study was carried out in the Pathology section of a referral Brazilian thyroid cancer center. Methods and Patients: A consecutive series of almost 1000 patients submitted to thyroidectomy followed radioiodine ablation from 1990 to 2017 will be studied. The clinicopathological features will be considered for all patients including disease persistence at the end of follow up and disease-specific mortality. We expected obtained 200 specimens of thyroid tumors to be immunohistochemically investigated for PD-L1, Mcl-1 and Ki-67 expressions and them correlate to recurrence and dynamic response to therapy stratification. In addition, we hope analyzing the relationships between Mcl-1 expression and TERT promoter mutations, BRAF status and disease progression. Outcome measures: We expected an overexpression of PD-L1, Ki-67 and Mcl-1 markers in intermediate-high risk DTC cases correlated to clinicopathologic features as age, histological cancer type, biochemical or structural disease persistence and poor response to therapy in long follow-up. Identification of Mcl-1 expression concomitant to BRAF and/or TERT mutation may have direct therapeutic relevance to patients with advanced refractory thyroid cancer and new target therapies. (AU)