Author(s): Matos, Maria de Lurdes ; Pinto, Mafalda ; Alves, Marta ; Canberk, Sule ; Gonçalves, Ana ; Bugalho, Maria João ; Papoila, A.L. ; Soares, Paula
Date: 2024
Persistent ID: http://hdl.handle.net/10362/164575
Origin: Repositório Institucional da UNL
Subject(s): BRAF; differentiated thyroid carcinomas (DTCs); genetics; indeterminate nodules; papillary thyroid carcinomas (PTCs); RAS; TERT; ultrasound-guided fine needle aspiration cytology (US-FNAC); Clinical Biochemistry
Funding Information: This research received funding for SC, in the framework of a Ph.D. grant (SFRH/BD/147650/2019) supported by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT). This study is part of the project “Institute for Research and Innovation in Health Sciences” (UID/BIM/04293/2019) and the project “The Porto Comprehensive Cancer Center” ref. NORTE-01-0145-FEDER-072678—Consórcio PORTO.CCC—Porto. Comprehensive Cancer Center Raquel Seruca. Publisher Copyright: © 2024 by the authors.
Introduction: Molecular tests can contribute to improve the preoperative diagnosis of thyroid nodules. Tests available are expensive and not adapted to different populations. Aim: This study aimed to compare the cyto-histological genetic profile and to evaluate the reliability of molecular tests using ultrasound-guided fine needle aspiration cytology (US-FNAC) in accurately diagnosing differentiated thyroid carcinomas (DTCs) and predicting biologic behavior of papillary thyroid carcinomas (PTCs). Materials and Methods: The series included 259 patients with paired cyto-histological samples totaling 518 samples. The genetic alterations were analyzed via PCR/Sanger sequencing. The association with clinicopathologic features was evaluated in PTCs. Results/Discussion: From the 259 patients included, histologies were 50 (19.3%) benign controls and 209 (80.7%) DTC cases, from which 182 were PTCs; cytologies were 5.8% non-diagnostic, 18.2% benign, 39% indeterminate, and 37.1% malignant. In histology, indeterminate nodules (n = 101) were 22.8% benign and 77.2% malignant. Mutation frequencies in cytology and histology specimens were, respectively, TERTp: 3.7% vs. 7.9%; BRAF: 19.5% vs. 25.1%; and RAS: 11% vs. 17.5%. The overall cyto-histological agreement of the genetic mutations was 94.9%, with Cohen’s k = 0.67, and in indeterminate nodules agreement was 95.7%, k = 0.64. The identified mutations exhibited a discriminative ability in diagnosing DTC with a specificity of 100% for TERTp and BRAF, and of 94% for RAS, albeit with low sensitivity. TERTp and BRAF mutations were associated with aggressive clinicopathological features and tumor progression in PTCs (p < 0.001). The obtained good cyto-histological agreement suggests that molecular analysis via US-FNAC may anticipate the genetic profile and the behavior of thyroid tumors, confirming malignancy and contributing to referring patients to surgery.
