Immunohistochemical loss of LKB1 is a biomarker for more aggressive biology in KRAS mutant lung adenocarcinoma.

摘要: Purpose: LKB1 loss is common in lung cancer but no assay exists to efficiently evaluate presence or absence of LKB1. We validated an immunohistochemistry (IHC) for and determined the impact KRAS-mutant NSCLC. Experimental Design: optimized IHC (clone Ley37D/G6) using a panel cell lines tumors with known mutations, including 2 patients Peutz-Jeghers syndrome (PJS) who developed adenocarcinoma. retrospectively analyzed from 154 NSCLC patients, 123 smokers 31 never-smokers, correlated findings patient tumor characteristics clinical outcome. Results: expression was lost by 30% KRAS mutant (smokers 35% vs. never-smokers 13%, P=0.017). did not correlate specific mutation more frequent transversion mutations (P=0.029). concurrent had higher number metastatic sites at time diagnosis (median 2.5 2, P=0.01), incidence extra-thoracic metastases (P=0.01), brain metastasis frequently (48% 25%, P=0.02). There non-significant trend worse survival stage IV loss. Conclusions: reliable efficient samples smokers, associated aggressive phenotype accordingly preclinical models.