Snehal G Patel1, Sally E Carty1, Kelly L McCoy1, N Paul Ohori2, Shane O LeBeau3, Raja R Seethala2, Marina N Nikiforova2, Yuri E Nikiforov2, Linwah Yip4. 1. Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, PA. 2. Department of Pathology, University of Pittsburgh, Pittsburgh, PA. 3. Department of Medicine, Division of Endocrinology, University of Pittsburgh, Pittsburgh, PA. 4. Department of Surgery, Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, PA. Electronic address: yipl@upmc.edu.
Abstract
BACKGROUND: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy. METHODS: Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay. RESULTS: In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83%). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No preoperative variables were associated with malignancy including age (P = .07), sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49), nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P = .24), multifocality (P = .23), or presence of ≥1 suspicious feature (P = .86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease. CONCLUSION: Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation.
BACKGROUND: Preoperative detection of RAS mutations can contribute to cancer risk assessment in indeterminate thyroid nodules, although RAS is not always associated with malignancy. METHODS: Fine-needle aspiration samples classified in 1 of 3 indeterminate cytology categories were prospectively tested for N-, H-, and K-RAS mutations using next-generation sequencing assay. RESULTS: In the study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86 patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76% of RAS-positive nodules were malignant and follicular variant papillary thyroid cancer was the most common cancer type (83%). HRAS mutations had the greatest risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No preoperative variables were associated with malignancy including age (P = .07), sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49), nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P = .24), multifocality (P = .23), or presence of ≥1 suspicious feature (P = .86). Only 60% of patients with a unifocal nodule on ultrasound had single focus low-risk encapsulated follicular variant papillary thyroid cancer or benign disease. CONCLUSION: Preoperative RAS mutation detection in thyroid nodules carries a substantial risk of cancer with a greater risk associated with HRAS and NRAS. Most RAS malignancies are follicular variant papillary thyroid cancer, which may inform the extent of operation.
Authors: Lisa A Radkay; Simion I Chiosea; Raja R Seethala; Steven P Hodak; Shane O LeBeau; Linwah Yip; Kelly L McCoy; Sally E Carty; Karen E Schoedel; Marina N Nikiforova; Yuri E Nikiforov; N Paul Ohori Journal: Cancer Cytopathol Date: 2014-08-12 Impact factor: 5.284
Authors: F Basolo; F Pisaturo; L E Pollina; G Fontanini; R Elisei; E Molinaro; P Iacconi; P Miccoli; F Pacini Journal: Thyroid Date: 2000-01 Impact factor: 6.568
Authors: Linwah Yip; Marina N Nikiforova; Jenny Y Yoo; Kelly L McCoy; Michael T Stang; Michaele J Armstrong; Kristina J Nicholson; N Paul Ohori; Christopher Coyne; Steven P Hodak; Robert L Ferris; Shane O LeBeau; Yuri E Nikiforov; Sally E Carty Journal: Ann Surg Date: 2015-09 Impact factor: 12.969
Authors: Yuri E Nikiforov; David L Steward; Toni M Robinson-Smith; Bryan R Haugen; Joshua P Klopper; Zhaowen Zhu; James A Fagin; Mercedes Falciglia; Katherine Weber; Marina N Nikiforova Journal: J Clin Endocrinol Metab Date: 2009-03-24 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: Pablo Valderrabano; Melissa J McGettigan; Cesar A Lam; Laila Khazai; Zachary J Thompson; Christine H Chung; Barbara A Centeno; Bryan McIver Journal: Thyroid Date: 2018-07-17 Impact factor: 6.568
Authors: Pablo Valderrabano; Laila Khazai; Zachary J Thompson; Marino E Leon; Kristen J Otto; Julie E Hallanger-Johnson; J Trad Wadsworth; Bruce M Wenig; Christine H Chung; Barbara A Centeno; Bryan McIver Journal: Thyroid Date: 2017-09-14 Impact factor: 6.568
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
Authors: Joshua R Krasner; Nourah Alyouha; Marc Pusztaszeri; Veronique-Isabelle Forest; Michael P Hier; Galit Avior; Richard J Payne Journal: J Otolaryngol Head Neck Surg Date: 2019-10-17