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Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas.
Endocr Pathol 2016; 27(2):153-61EP

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+Show Affiliations

Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. semen_yesil@yahoo.com.tr.Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of Pathology, Gulhane Military Medical Academy, Haydarpasa Training Hospital, Istanbul, Turkey.Department of Pediatric Endocrinology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of Nuclear Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26951110

Citation

Onder, Semen, et al. "Classic Architecture With Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations Are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas." Endocrine Pathology, vol. 27, no. 2, 2016, pp. 153-61.
Onder S, Ozturk Sari S, Yegen G, et al. Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas. Endocr Pathol. 2016;27(2):153-61.
Onder, S., Ozturk Sari, S., Yegen, G., Sormaz, I. C., Yilmaz, I., Poyrazoglu, S., ... Mete, O. (2016). Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas. Endocrine Pathology, 27(2), pp. 153-61. doi:10.1007/s12022-016-9420-0.
Onder S, et al. Classic Architecture With Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations Are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas. Endocr Pathol. 2016;27(2):153-61. PubMed PMID: 26951110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas. AU - Onder,Semen, AU - Ozturk Sari,Sule, AU - Yegen,Gulcin, AU - Sormaz,Ismail Cem, AU - Yilmaz,Ismail, AU - Poyrazoglu,Sukran, AU - Sanlı,Yasemin, AU - Giles Senyurek,Yasemin, AU - Kapran,Yersu, AU - Mete,Ozgur, PY - 2016/3/9/entrez PY - 2016/3/10/pubmed PY - 2017/2/25/medline KW - BRAF V600E KW - Papillary thyroid carcinoma KW - Pediatric thyroid cancer KW - TERT KW - Well differentiated thyroid carcinoma SP - 153 EP - 61 JF - Endocrine pathology JO - Endocr. Pathol. VL - 27 IS - 2 N2 - 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. SN - 1559-0097 UR - https://www.unboundmedicine.com/medline/citation/26951110/Classic_Architecture_with_Multicentricity_and_Local_Recurrence_and_Absence_of_TERT_Promoter_Mutations_are_Correlates_of_BRAF__V600E__Harboring_Pediatric_Papillary_Thyroid_Carcinomas_ L2 - https://dx.doi.org/10.1007/s12022-016-9420-0 DB - PRIME DP - Unbound Medicine ER -