Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea

Abstract

Background: Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non-small cell lung cancers (NSCLCs). Methods: A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images. Results: In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively. Conclusions: BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.

BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients

“…Similar results were shown by Hofman et al, suggesting that VE1 staining is a rapid, specific and very sensitive method [ 23 ]. In addition, Chang et al reported that VE1 immunohistochemistry showed almost perfect interobserver agreement, suggesting that this could be a screening test for BRAF mutation [ 24 ]. In present study, BRAF V600E mutated cases showed diffuse (100% of proportion) positivity, though the intensity was heterogeneous in two cases.…”

Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review

“…In brief, 4 µm thick FFPE tissue sections were deparaffinized and rehydrated using a xylene and alcohol solution. We used an automated instrument (BOND-MAX immunostainer; Leica Biosystems, Deer Park, IL, USA) with a biotin-free polymeric horseradish peroxidase-linker antibody conjugate system (BOND Polymer Intense Detection System; Leica Biosystems) [33][34][35][36]. After antigen retrieval, endogenous peroxidases were quenched with hydrogen peroxide.…”

Mesonephric-like Adenocarcinoma of the Uterine Corpus: Clinicopathological and Prognostic Significance of L1 Cell Adhesion Molecule (L1CAM) Over-expression

“…Tissue sections from the corresponding formalin-fixed, paraffin-embedded blocks were mounted onto SuperFrost Plus Microscope Slides (Thermo Fisher Scientific, Waltham, MA, USA), deparaffinized in xylene, and then rehydrated using an ethanol gradient. Immunohistochemical staining was carried out using a Bond-Max automated immunostainer (Leica Biosystems, Lincolnshire, IL, USA) and a Bond Polymer Refine Detection System (Leica Biosystems), as described previously (11,30,(35)(36)(37)(38)(39). Following antigen retrieval, the slides were incubated with a primary antibody against L1CAM (dilution 1:100, clone EPR18998, Abcam, Waltham, MA, USA).…”