E Macerola1, T Rago2, A Proietti3, F Basolo1, P Vitti4. 1. Department of Surgical, Medical, Molecular Pathology and Critical Area (Anatomical Pathology Section), University of Pisa, via Savi 10, 56126, Pisa, Italy. 2. Department of Clinical and Experimental Medicine (Endocrinology Section), University of Pisa, via Paradisa 2, 56124, Pisa, Italy. 3. Division of Anatomical Pathology, University Hospital of Pisa, via Roma 57, 56126, Pisa, Italy. 4. Department of Clinical and Experimental Medicine (Endocrinology Section), University of Pisa, via Paradisa 2, 56124, Pisa, Italy. paolo.vitti@med.unipi.it.
Abstract
PURPOSE: Fine-needle aspiration (FNA) cytology is a mainstay in the evaluation of thyroid nodules, but fails to reach reliable results in 25-30% of cases. The role of molecular markers in helping clinical decisions has been investigated for the last years, but their clinical usefulness is still unsettled. METHODS: Mutation analysis of BRAF, RAS genes and TERT promoter was performed in a series of 617 consecutive cytological specimens undergoing FNA. RESULTS: The 617 nodules had the following cytological diagnosis: non diagnostic 22 (3.6%), benign 425 (68.9%), indeterminate 114 (18.5%), suspicious 11 (1.8%) and malignant 45 (7.3%). BRAF mutations were found in 31 cases (5.0%), all but two in suspicious and malignant nodules. RAS mutations were detected in 47 samples (7.6%): 25 benign (5.9%) and 19 indeterminate nodules (16.7%). TERT promoter mutation alone was detected in three samples. Histological outcome was available for 167 nodules, 81 of which proved malignant: all the 48 with suspicious or malignant cytology; 25 out of 56 (44.6%) with indeterminate and 8 out of 57 (14%) with benign cytology. BRAF mutations were associated with worse tumors pathological features. The presence of RAS mutations was indicative of follicular-patterned malignancies in 5 out of 8 benign nodules and 9 out of 11 indeterminate nodules. CONCLUSIONS: Our study established mutational rates for BRAF and RAS genes in a large series of FNA specimens. BRAF mutations were confirmed as highly specific but not able to improve cytological diagnosis, while RAS testing proved effective in assessing malignancy in nodules with indeterminate and benign cytology.
PURPOSE: Fine-needle aspiration (FNA) cytology is a mainstay in the evaluation of thyroid nodules, but fails to reach reliable results in 25-30% of cases. The role of molecular markers in helping clinical decisions has been investigated for the last years, but their clinical usefulness is still unsettled. METHODS: Mutation analysis of BRAF, RAS genes and TERT promoter was performed in a series of 617 consecutive cytological specimens undergoing FNA. RESULTS: The 617 nodules had the following cytological diagnosis: non diagnostic 22 (3.6%), benign 425 (68.9%), indeterminate 114 (18.5%), suspicious 11 (1.8%) and malignant 45 (7.3%). BRAF mutations were found in 31 cases (5.0%), all but two in suspicious and malignant nodules. RAS mutations were detected in 47 samples (7.6%): 25 benign (5.9%) and 19 indeterminate nodules (16.7%). TERT promoter mutation alone was detected in three samples. Histological outcome was available for 167 nodules, 81 of which proved malignant: all the 48 with suspicious or malignant cytology; 25 out of 56 (44.6%) with indeterminate and 8 out of 57 (14%) with benign cytology. BRAF mutations were associated with worse tumors pathological features. The presence of RAS mutations was indicative of follicular-patterned malignancies in 5 out of 8 benign nodules and 9 out of 11 indeterminate nodules. CONCLUSIONS: Our study established mutational rates for BRAF and RAS genes in a large series of FNA specimens. BRAF mutations were confirmed as highly specific but not able to improve cytological diagnosis, while RAS testing proved effective in assessing malignancy in nodules with indeterminate and benign cytology.
Authors: Emmanuel Labourier; Alexander Shifrin; Anne E Busseniers; Mark A Lupo; Monique L Manganelli; Bernard Andruss; Dennis Wylie; Sylvie Beaudenon-Huibregtse Journal: J Clin Endocrinol Metab Date: 2015-05-12 Impact factor: 5.958
Authors: Yuri E Nikiforov; Sally E Carty; Simon I Chiosea; Christopher Coyne; Umamaheswar Duvvuri; Robert L Ferris; William E Gooding; Steven P Hodak; Shane O LeBeau; N Paul Ohori; Raja R Seethala; Mitchell E Tublin; Linwah Yip; Marina N Nikiforova Journal: Cancer Date: 2014-09-10 Impact factor: 6.860
Authors: Whitney S Goldner; Trevor E Angell; Sallie Lou McAdoo; Joshua Babiarz; Peter M Sadow; Fadi A Nabhan; Christian Nasr; Richard T Kloos Journal: Thyroid Date: 2019-09-27 Impact factor: 6.568