Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma

Abstract

// Lianghong Teng 1, 2 , Wanglong Deng 3 , Junliang Lu 1 , Jing Zhang 1 , Xinyu Ren 1 , Huanli Duan 1 , Shannon Chuai 3 , Feidie Duan 3 , Wei Gao 2 , Tao Lu 1 , Huanwen Wu 1 , Zhiyong Liang 1 1 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China 2 Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China 3 Burning Rock Biotech Co. Ltd., Guangzhou, China Correspondence to: Zhiyong Liang, email: liangzhiyong1220@yahoo.com Huanwen Wu, email: whw14093@163.com Keywords: papillary thyroid carcinoma, hobnail variant, next-generation sequencing, molecular features, TERT promoter mutation Received: December 06, 2016     Accepted: January 24, 2017     Published: February 28, 2017 ABSTRACT Background: As a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear. Results: The prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation. Methods: HVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Conclusion: As an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.