Caracterização clínica e molecular de pacientes com carcinoma medular de tireoide do estado da Bahia

Abstract

Introduction: Medullary carcinoma of the thyroid (MCT) is a rare cancer that originates from C cells and may be sporadic (75%) or hereditary (25%) as a component of multiple endocrine neoplasia syndrome. Both sporadic disease and hereditary disease are due to mutations in the RET protooncogene mainly. MCT incidence and its molecular basis is still unknown and little investigated, especially in the northeastern states of the country. In Bahia, there are still no records of studies that have investigated the behavior and characteristics of this disease in the region. Objective: To characterize clinically and molecularly patients with MCT in the state of Bahia. Methodology: Cross-sectional and descriptive study involving patients with histopathological diagnosis of MCT which were submitted to DNA analysis from 2020 to 2022. Clinical pathology data were collected from the patients' anatomopathological and immunohistochemical reports. Genomic DNA was extracted from peripheral blood. Exons 10, 11, 13, 14 and 15 from the RET were amplified by Polymerase Chain Reaction (PCR) and subsequently they were sequenced by the Sanger method. Results: Clinical data: 29 patients were included in the study (82.8% female). The mean age from diagnosis was 46.5 ± 13.1 years and mean tumor size was 2.1 ± 1.4 cm. Capsular, blood vessel and lymphatic invasion and extrathyroidal invasion occurred in 13.8%, 6.9% and 3.4% of cases, respectively. According to the TNM classification, 38% of the tumors were staged as T1a, 27.6% T1b, 24.1% T2 and 10.3% T3. Regional lymph node metastasis (N1) was present in 44.8% of cases. The presence of distant metastasis (M1) to the mediastinum was observed in one case (3.4%). RET protooncogene variants were identified in 55.2% of patients. The pathogenic variant C634R was identified in one patient (3.4%). RET polymorphisms were identified in 51.7% of patients, from which L769L was the most frequent polymorphism. Discussion: RET C634R is associated with the diagnosis of multiple endocrine neoplasia type 2A and it is described in literature of the area as the most frequent pathogenic variant (30-50%) among affected patients. Conclusion: The study described unprecedentedly the clinical and molecular profile of patients with medullary carcinoma of the thyroid in Bahia. A germline pathogenic variant of RET was identified confirming the diagnosis of multiple endocrine neoplasia type 2A in one patient. RET protooncogene polymorphisms were identified in 51.7% of patients.