title: Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas.
abstract: This study is aimed to investigate the BRAF (V600E) and TERT promoter mutation profile of 50 pediatric papillary thyroid carcinomas (PTCs) to refine their clinicopathological correlates. The median age at the time of surgery was 16 years (range, 6-18). No TERT promoter mutations were identified in this series. The BRAF (V600E) mutation was present in 15 (30 %) tumors. From genotype-histologic variant correlation perspective, 13 of 24 classic variant PTCs and 2 of 7 diffuse sclerosing variant PTCs were found to harbor BRAF (V600E) mutation. One cribriform-morular variant, 3 solid variant, and 15 follicular variant PTCs were BRAF wild type. While tumors with distant metastasis were BRAF wild type, two of five tumors with extrathyroidal extension (ETE) harbored BRAF (V600E) mutation. Nine of 15 BRAF (V600E) harboring tumors had central lymph node metastases. There was no significant correlation with BRAF (V600E) mutation and age, gender, tumor size, ETE, central lymph node metastasis, the status of pT, pN1a-b, and distant metastasis. An adverse correlation between BRAF (V600E) mutation and disease-free survival (DFS) was noted in the entire cohort; however, the predictive value of BRAF (V600E) mutation disappeared within the group of tumors displaying classic architecture as well as classic variant PTCs. The present cohort identifies that the classic architecture with multicentricity and local recurrence are correlates of BRAF (V600E) harboring pediatric PTCs. While the small size of this cohort is one of the limitations, neither the BRAF mutation status nor the classic tumor architecture does seem to be an independent prognosticator of DFS in this series. Evidence also suggests that TERT promoter mutations do not seem to play a major role in the pathogenesis of pediatric PTCs.
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. semen_yesil@yahoo.com.tr.
authors.forename: Semen
authors.initials: S
authors.lastname: Onder
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Ozturk Sari
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Yegen
authors.affiliation: Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ismail Cem
authors.initials: IC
authors.lastname: Sormaz
authors.affiliation: Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Yilmaz
authors.affiliation: Department of Pediatric Endocrinology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Sukran
authors.initials: S
authors.lastname: Poyrazoglu
authors.affiliation: Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Sanlı
authors.affiliation: Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Giles Senyurek
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Yersu
authors.initials: Y
authors.lastname: Kapran
authors.affiliation: Department of Pathology, University Health Network, Toronto, ON, Canada. ozgur.mete2@uhn.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. ozgur.mete2@uhn.ca.|Endocrine Oncology Site Group, Princess Margaret Cancer Center, Toronto, ON, Canada. ozgur.mete2@uhn.ca.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Mete
mesh_terms: D000293:Adolescent; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009154:Mutation; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase
keywords: BRAF V600E; Papillary thyroid carcinoma; Pediatric thyroid cancer; TERT; Well differentiated thyroid carcinoma