Real-world assessment of the BRAF status in non-squamous cell lung carcinoma using VE1 immunohistochemistry: A single laboratory experience (LPCE, Nice, France)

Abstract

International guidelines recommend BRAF mutational status assessment in treatment-naive advanced non-squamous non-small cell lung carcinoma (NSCLC) patients since the presence of a BRAFV600 mutation enables specific BRAF inhibitor treatment. For this purpose, the mutational status needs to be obtained in 10 working days. Herein, we prospectively evaluated the feasibility of systematic assessment of the BRAF status using immunohistochemistry (IHC) in a single institution (LPCE, Nice) at baseline for NSCLC diagnosed. Methods: 1317 NSCLC were evaluated using BRAF IHC from 2011 to 2019. Initially the BRAF status was prospectively assessed using NGS and/or pyrosequencing in 618 consecutively diagnosed NSCLC patients from 2012 to 2016; BRAFV600E and BRAF nonV600E mutated tumors detected in this cohort were retrospectively evaluated using BRAF IHC. Secondarily, 699 biopsies of NSCLC were prospectively analyzed between 2017 and 2019 using BRAF IHC. BRAF IHC positive tumors were tested using a rapid BRAF specific PCR based assay. Results: Initially, 21/618 (3%) of tumors (15 early and 6 late stage tumors) were BRAFV600E mutated according to the results of NGS and/or pyrosequencing. BRAF IHC was positive in 21/21 of these cases and negative in 51/ 51 (100 %) BRAF non V600E mutated cases. In the prospective BRAF IHC tested cohort of patients, 24/699 (3%) tumors (13 early and 11 late stage tumors) were positive with VE1 IHC. The BRAF PCR assay was positive in 20/ 24 (83 %) of these cases. Conclusion: BRAFV600E IHC screening of treatment-naïve NSCLC patients is a rapid, specific and very sensitive method which can lead in advanced stage positive NSCLC tumors to a BRAF inhibitor treatment. This test can be routinely integrated into mandatory predictive biomarker 'testing of NSCLC. According to the organization of patient care and the physician's request, this practice can be proposed as an alternative to NGS-based tissue biopsy made at baseline.

Selection Strategies and Practical Application of BRAF V600E-Mutated Non–Small Cell Lung Carcinoma

“…The VE1 antibody was known to have a sensitivity of 82%–100% and a specificity of 95.2%–100% in detecting BRAF V600E mutation [ 26 , 27 ]. We also verified good sensitivity (90%) and specificity (92%) of the VE1 antibody.…”

BRAF as a positive predictive biomarker: Focus on lung cancer and melanoma patients

“…Interestingly, in 20 out of 24 cases (83 %) a fully-automated real-time PCR (RT-PCR) approach (Idylla, Biocartis, Mechelen, Belgium) confirmed the BRAF mutational status. The Authors explain that the four negative cases may be false-negative results of RT-PCR due to a low tumor cell content (1-5%) with less than a total of 50 tumor cells observed in the tissue sections (Hofman et al, 2020).…”

“…Overall, in a retrospective series previously evaluated by NGS and/or pyrosequencing, IHC was able to correctly identify all BRAF exon 15 p.V600E mutated patients. Interestingly, no false positives were observed among wild-type and BRAF non-p.V600E patients (Hofman et al, 2020). An important advantage in terms of TAT has been reported for IHC (three days) compared to pyrosequencing (five days) and NGS (14 days) (Hofman et al, 2020).…”

“…Interestingly, no false positives were observed among wild-type and BRAF non-p.V600E patients (Hofman et al, 2020). An important advantage in terms of TAT has been reported for IHC (three days) compared to pyrosequencing (five days) and NGS (14 days) (Hofman et al, 2020). In the prospective cohort, BRAF IHC testing showed a positive result in 24 (3%) out of 699 tumors.…”

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…The frequency of BRAFV600 mutations seems lower in Hispanic and Asian patients than in Caucasians [53,87]. BRAFV600 mutations can be detectable in tissue biopsy and in cytological samples using RT-PCR and V600E IHC/ICC approaches or via NGS [88,89]. In plasma samples, BRAFV600 mutations can be detectable via RT-PCR or NGS [67,90].…”