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Horm Metab Res 2009; 41(6): 482-487
DOI: 10.1055/s-0029-1215558
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Lack of Correlation between BRAF V600E Mutational Status and the Expression Profile of a Distinct Set of miRNAs in Papillary Thyroid Carcinoma

S-Y. Sheu 1 , F. Grabellus 1 , S. Schwertheim 1 , S. Handke 1 , K. Worm 1 , K. W. Schmid 1 , 2
  • 1Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
  • 2Member of the West German Cancer Centre Essen (WTZE), Essen, Germany
Further Information

Publication History

received 13.01.2009

accepted 11.02.2009

Publication Date:
15 April 2009 (online)

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Abstract

Recent studies demonstrated a significant upregulation of distinct microRNAs (miRNAs), small endogenous RNAs that regulate gene expression, in papillary thyroid carcinoma (PTC). In the pathogenesis of PTC the T1799A (V600E) BRAF mutation is the most common genetic alteration leading to a constitutive activation of the MAPK pathway. The aim of the present study was to elucidate a possible correlation between BRAF mutational status and a distinct miRNA expression profile. In a series of 221 PTC we determined the BRAF V600E mutational status using DNA-sequencing and correlated the occurrence of the mutation with a variety of clinicopathologcial data. The miRNA expression profile of five selected subtypes (miRNA-146b, −181b, −21, −221, −222) in two matched cohorts of BRAF positive (n=28) and wildtype cases (n=26) was examined by RT-PCR TaqMan miRNA assay. The BRAF V600E mutation was significantly found in PTCs with extrathyroidal extension (p <0.001). Among them, V600E was even significantly associated with smaller tumour size of 1 cm or less (microcarcinomas; p<0.003) and the follicular (p=0.017) and tall cell variant (p=0.015). By calculating relative changes in miRNA gene expression no differences in fold changes could be detected between BRAF positive and wildtype PTC suggesting that BRAF has no regulatory influence on the expression of the five examined miRNAs. However, our study confirmed the diagnostic utility of this distinct set of miRNAs to detect PTC by significant fold changes in at least 3 miRNAs (miRNA-146b, −221, −222) irrespective of its histological variant.

Key words

miRNA - BRAF - papillary thyroid carcinoma

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Correspondence

K. W. Schmid MD, MRCPath 

Institute of Pathology and Neuropathology

University Hospital of Essen

University of Duisburg-Essen

Hufelandstr. 55

45122 Essen

Germany

Phone: +49/201/723/2890

Fax: +49/201/723/5926

Email: kw.schmid@uk-essen.de