J Pathol Transl Med.  2022 Nov;56(6):334-341. 10.4132/jptm.2022.08.22.

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

Affiliations
  • 1Department of Pathology, Inje University Ilsan Paik Hospital, Goyang, Korea
  • 2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 3Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
  • 4Department of Pathology, National Cancer Center, Goyang, Korea
  • 5Department of Pathology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, 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.

Keyword

V600E; Observer variation; Predictive value of tests; Immunohistochemistry; Adenocarcinoma of lung

Figure

  • Fig. 1. BRAF VE1 expression was observed in the cytoplasm of tumor cells. Negative (A), weak (1+) (B), moderate (2+) (C), and strong (3+) (D) VE1 expression.

  • Fig. 2. Receiver operating characteristic curve. AUC, area under the curve; CI, confidence interval.

  • Fig. 3. BRAF expression in the discrepant cases. (A) Case 7 showing questionable cytoplasmic staining of faint intensity. (B) Case 14 showing no cytoplasmic staining. (C) Case 22 showing weak but diffuse cytoplasmic staining. (D) Case 24 showing heterogeneous weak to moderate staining within individual glands.


Reference

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