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Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis

Abstract

The evaluation of surgically resected papillary thyroid carcinomas (PTC) by immunohistochemistry (IHC) for BRAF mutation has diagnostic, prognostic and therapeutic implications. The goal of this meta-analysis was to perform a systematic review of studies using the VE1 clone (specific for detection of the BRAF V600E mutation) on formalin-fixed paraffin embedded (FFPE) thyroid surgical resection specimens for primary papillary thyroid carcinoma. The authors’ molecular techniques, immunohistochemistry protocols, and scoring methods for VE1 immunostaining were also evaluated. This study included 4079 PTCs representing data from 23 studies. The results extracted from each study were split into two different groups, direct sequencing group or PCR group, based on the molecular “gold standard” method used to compare VE1 IHC staining. In the direct sequencing group, the IHC sensitivity was 100% (95% CI 0.97–1.00) and specificity 84% (95% 0.72–0.91). In the PCR group the sensitivity was 98% (95% CI 0.96–0.99) and specificity 89% (95% CI 0.82–0.94). Although immunohistochemical procedures varied by author, the overall performance of the VE1 clone shows that it is highly sensitive and relatively specific for detecting the BRAF V600E mutation in surgical resection specimens. However, standardization of immunohistochemical procedural method and scoring/interpretation criteria may improve the reliability and reproducibility for the use of VE1 clone for future practice.

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Acknowledgements

The authors would like to give special thanks to Dr. Girish Venkataraman (University of Chicago, Director of the Immunohistochemistry Lab in the Department of Pathology, Section of Hematopathology) for his guidance regarding BRAF immunohistochemical techniques.

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Correspondence to Kyle G. Parker.

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Parker, K.G., White, M.G. & Cipriani, N.A. Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis. Head and Neck Pathol 14, 1067–1079 (2020). https://doi.org/10.1007/s12105-020-01166-8

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  • DOI: https://doi.org/10.1007/s12105-020-01166-8

Keywords

  • Papillary thyroid carcinoma
  • Immunohistochemistry
  • BRAFV600E
  • Meta-analysis