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Employing Digital Droplet PCR to Detect BRAF V600E Mutations in Formalin-fixed Paraffin-embedded Reference Standard Cell Lines
Published on: October 8, 2015
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Morphology predicts BRAF (V⁶⁰⁰E) mutation in papillary thyroid carcinoma: an interobserver reproducibility study.
Renu K Virk1, Constantine G A Theoharis, Avinash Prasad
1Department of Pathology, Yale School of Medicine, 310 Cedar Street, LH-108, New Haven, CT, 06520, USA.
Virchows Archiv : an International Journal of Pathology
|February 20, 2014
Summary
Morphological features of papillary thyroid carcinoma (PTC) can accurately predict BRAF (V600E) mutations. This study shows high accuracy and interobserver agreement in predicting these mutations based on H&E-stained slides.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Papillary thyroid carcinoma (PTC) harbors specific morphological features when associated with the BRAF (V600E) mutation.
- These features include classic or tall cell variants, infiltrative borders, desmoplasia/fibrosis, psammoma bodies, and distinct nuclear characteristics.
Purpose of the Study:
- To investigate the predictive accuracy of morphological features for BRAF (V600E) mutation in PTC.
- To assess the interobserver reproducibility of this morphological prediction.
Main Methods:
- Analysis of Hematoxylin and eosin-stained sections from 50 PTCs (26 mutation-positive, 24 mutation-negative).
- Evaluation of specific morphological features like tumor borders, desmoplasia, psammoma bodies, and nuclear characteristics.
- Interobserver reproducibility assessment by two pathologists on 30 PTCs, blinded to mutational status.
Main Results:
- BRAF (V600E) mutation was predicted with 84% accuracy (96% sensitivity, 71% specificity).
- Subtle nuclear features and well-circumscribed, non-infiltrative borders showed high negative predictive values (100% and 95%, respectively).
- The combination of infiltrative borders, desmoplasia, and psammoma bodies reached 100% positive predictive value. Interobserver agreement was substantial (κ=0.79, 83% accuracy).
Conclusions:
- Morphological assessment of PTCs can reliably predict BRAF (V600E) mutation status.
- The findings support the use of histopathology for preliminary identification of BRAF (V600E) mutations, aiding in diagnostic and potentially therapeutic decisions.
- High interobserver agreement suggests this predictive method is robust and reproducible.
