Abstract
BRAF V600E mutation, a missense mutation in exon 15 resulting in valine substitution for glutamate at position 600 within the kinase domain of BRAF oncogene, is found in a subset of lung adenocarcinoma (ADC). The usefulness of immunohistochemistry (IHC) as an alternative diagnostic tool has not been validated. Moreover, the clinical information of patients with BRAF V600E-mutated lung ADC is limited. We retrospectively identified 31 lung ADCs diagnosed with BRAF V600E mutation by standard molecular sequencing methods and reviewed their clinical characteristics and pathological features. An anti-BRAF V600E monoclonal VE1 antibody for IHC was used to confirm the expression patterns. The series was comprised of 99 cases, 29 with BRAF V600E mutation and 70 without BRAF V600E but with other types or undetected mutations. The majority of BRAF V600E-mutated biopsied tissues were poorly differentiated and micropapillary patterns. Application of the IHC VE1 assay was highly feasible in primary/metastatic sites or effusion blocks, yielding positive findings in 28 of 29 (96.6%) BRAF V600E-mutated tumors and negative results in 69 of 70 (98.6%) tumors harboring other types or undetected mutations. Patients who received pemetrexed/platinum-based rather than mutation-targeted chemotherapy as the first-line therapy for metastatic disease showed median overall survival of 15.5 months. Our findings indicated that VE1 antibody-based IHC analysis demonstrated high sensitivity and specificity to detect BRAF V600E-mutated lung ADCs in tissues from primary or metastatic sites.
Highlights
insertion. * (Ins) the past decade, individualizing molecular targeted therapy based on specific driver oncogene aberrations has provided a powerful and favorable approach to the treatment of non-small cell lung cancer (NSCLC) [1,2,3]
None of the patients were identified as having concurrent BRAF
For the first-line treatments, pemetrexed-platinum considered as a false positive case
Summary
In the past decade, individualizing molecular targeted therapy based on specific driver oncogene aberrations has provided a powerful and favorable approach to the treatment of non-small cell lung cancer (NSCLC) [1,2,3]. One of the important driver gene mutations, which leads to signaling pathway dysregulation in lung cancer, occurs in v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) [4]. A thymine to adenine single-base change at position 1799 in exon 15, which results in the V600E mutation, is observed in 1–2% of lung ADC [6]. This mutation has been shown to exhibit higher basal kinase activity than that of the wild-type protein [7], and increase transforming capacity in NIH3T3 cells [8].
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