Investigation of patterns of nodal metastases in BRAF mutant lung cancer

Abstract

Axillary lymph nodes (axLN) are a rare site of nodal metastases in patients with lung cancer. BRAF mutated lung cancer is a genetically distinct subtype that occurs in 2–5% of non-small cell lung carcinomas (NSCLC). A recent study identified a highly unusual pattern of metastatic spread to axLN in patients with BRAF mutated colorectal cancer (CRC). The purpose of the study is to assess the incidence of axLN metastases in BRAF mutated NSCLC. Baseline computed tomography (CT) imaging at diagnosis and all follow up CTs of patients with BRAF mutated NSCLC treated at our institution were retrospectively reviewed by two radiologists for evidence of axLN metastases. Positron emission tomography (PET)/CT was reviewed when available. A control group of patients with non-BRAF mutated NSCLC was assessed. Three criteria were used for the diagnosis of a metastatic node; pathologic confirmation, radiologic size greater ≥1.5 cm in short axis diameter or fluorodeoxyglucose avidity on PET/CT and radiologic size ≥1.0 cm in short axis diameter. Forty-six patients with BRAF mutated NSCLC and CT images on the institutional PACS were identified. 7 (15%) patients with BRAF mutated NSCLC had axLN metastases using the proposed diagnostic criteria. One patient had a pathologic proven axLN metastasis, 3 had axLNs measuring ≥ 1.5cm in short axis, and 3 had nodes which were FDG avid on PET/CT and measured ≥1.0cm in short axis. By comparison, 1 of 46 (2%) control patients with non-BRAF mutated NSCLC had axLN metastases. Previous series have reported the prevalence of axLN metastases in patients with NSCLC as 0.61% –0.75%. We have found a higher incidence of axLN metastases in BRAF mutated NSCLC patients than described in non-BRAF mutated NSCLC patients. Examination of the axilla should be a routine part of physical examination in this genetically distinct subgroup of lung cancer patients.

Novel mutational landscapes and expression signatures of lung squamous cell carcinoma

“…ZEB2 expression increased in NSCLC [ 22 ] and it can induce epithelial-mesenchymal transition (EMT) to facilitate the metastasis of cancer cells [ 23 , 24 ]. BRAF mutated lung cancer is a genetically distinct subtype that accounts for about 5% of NSCLC [ 25 ]. IGF2R is mutated frequently in LUSC and it suppresses cancer cell growth [ 26 ].…”

Validation of Immunohistochemistry for the Detection of BRAF V600E-Mutated Lung Adenocarcinomas

“…Therefore, more studies need to be conducted to elucidate whether IHC with the VE1 antibody might be suitable as an alternative method to detect BRAF V600E mutation in patient with lung ADC. Moreover, the clinical characteristics of patients with lung cancer carrying BRAF V600E mutation are not consistent across different studies [18,19,20]. In addition, little is known regarding the real-world clinical outcomes of current treatments in patients not receiving BRAF-targeted therapies.…”

Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF‐mutation status?

“…3,6,18,19 Former studies revealed that NSCLC patients harboring BRAF V600E mutations occurred predominantly in females with a never-smoking history, while non-V600 mutations were mainly found in male smokers. 17,20,21 In cohort 2, most patients (93.8%) harboring BRAF V600E mutation never had a smoking history. In contrast, most patients (83.3%) harboring BRAF mutations in cohort 1 had a smoking history.…”