Clinico-morphological characteristics of SMARCA4-deficient lung cancer

Abstract

Background. Mutations in the SMARCA4 gene of the SWI/SNF chromatin remodeling complex occur in 10% of nonsmall cell lung cancer (NMRL). SMARCA4-deficient lung tumors are aggressive neoplasm with poor outcome. Morphological, immunohistochemical and clinical description of this tumor type is lacking.The aim of the study was to investigate clinical and morphological characteristics and frequency of SMARCA4 expression loss in patients with lung tumors.Material and methods. Specimens from a total 100 non-small cell lung cancer cases were immunohistochemically examined for expression of SMARCA4 and SMARCA2. EGFR, BRAF mutations and gene rearrangement of ALK or ROS1 were tested by immunohistochemical, PCR-based or FISH techniques among cases with loss of SMARCA4 expression.Results. Loss of SMARCA4 expression was detected in 14 (14%) cases. Most of them are men — 93%. The average age was 63 years. In most cases (64%) SMARCA4-deficient tumors have been diagnosed as adenocarcinoma. The mutation was significantly associated with smoking history (p-value 0.009). Mutations in EGFR, BRAF genes and rearrangement of ALK or ROS1 in the SMARCA4-deficient tumor group have not been detected.Conclusion.  SMARCA4-deficient tumors are subgroup of NMRL, prevalent in smoking men and diagnosed as lung adenocarcinoma without activating mutations.