Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors

Lai, Wei-An; Liu, Chih-Yi; Lin, Shih-Yao; Chen, Chien-Chin; Hang, Jen-Fan

doi:10.3390/cancers12071973

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Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors

^1,3,

^4,5

and

Jen-Fan Hang

^1,6,*

Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan

Division of Pathology, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan

Department of Pathology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan

⁴

Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan

⁵

Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan

⁶

National Yang-Ming University School of Medicine, Taipei 112, Taiwan

Author to whom correspondence should be addressed.

Cancers 2020, 12(7), 1973; https://doi.org/10.3390/cancers12071973

Received: 25 June 2020 / Revised: 13 July 2020 / Accepted: 17 July 2020 / Published: 20 July 2020

(This article belongs to the Special Issue Biomarkers of Thyroid Cancer)

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Abstract

Anaplastic thyroid carcinoma (ATC) is rare but highly aggressive. We investigated the association of selected driver mutations, including BRAF, RAS, PIK3CA, TERT promoter, TP53, POLE, and mismatch repair deficiency (MMR-D) with the clinicopathological features of ATC to identify prognostic and predictive biomarkers. Thirty-nine retrospective cases from pathology archives were enrolled for clinicopathology analysis and immunohistochemistry, and 27 cases had sufficient specimens for further molecular testing using targeted next-generation sequencing and mass spectrometry. BRAF^V600E and RAS mutations were identified in 25.9% and 40.7% of ATC, respectively. BRAF^V600E mutation was significantly associated with coexisting papillary thyroid carcinoma (p = 0.009) and RAS mutations with female gender (p = 0.012). In univariant analysis, the non-BRAF/RAS tumors were significantly associated with the presence of a sarcomatoid pattern (p = 0.045). PIK3CA, TERT promoter, and TP53 mutations were identified in 14.8%, 81.5%, and 70.4% of cases, respectively. No MMR-D or POLE mutations were detected. In survival analyses, RAS and PIK3CA mutations were significantly associated with inferior outcomes (p = 0.03 and p = 0.006, respectively). In conclusion, driver mutations in ATC are associated with distinct clinicopathological features. RAS and PIK3CA mutations were negative predictors for patient survival. Emerging therapeutic agents targeting BRAF, RAS, and PI3 kinase may benefit a substantial proportion of ATC patients. View Full-Text

Keywords: anaplastic thyroid carcinoma; RAS; BRAF^V600E; PIK3CA; TERT promoter; TP53

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MDPI and ACS Style

Lai, W.-A.; Liu, C.-Y.; Lin, S.-Y.; Chen, C.-C.; Hang, J.-F. Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors. Cancers 2020, 12, 1973. https://doi.org/10.3390/cancers12071973

AMA Style

Lai W-A, Liu C-Y, Lin S-Y, Chen C-C, Hang J-F. Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors. Cancers. 2020; 12(7):1973. https://doi.org/10.3390/cancers12071973

Chicago/Turabian Style

Lai, Wei-An, Chih-Yi Liu, Shih-Yao Lin, Chien-Chin Chen, and Jen-Fan Hang. 2020. "Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors" Cancers 12, no. 7: 1973. https://doi.org/10.3390/cancers12071973

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Characterization of Driver Mutations in Anaplastic Thyroid Carcinoma Identifies RAS and PIK3CA Mutations as Negative Survival Predictors

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