Nuclear factor-κB (NF-κB) is frequently expressed in lung cancer and preneoplastic lesions

BACKGROUND. Nuclear factor-kappa B (NF-kappa B), a key transcription factor thought to play a major role in carcinogenesis, regulates many important signaling pathways involved in tumor promotion. Although NF-kappa B can be activated in lung cancer cell lines by tobacco exposure, there have been no studies of the expression of NF-kappa B in lung cancer pathogenesis. METHODS. The immunohistochemical expression of NF-kappa B p65 was investigated in 394 lung cancers (370 nonsmall cell lung carcinomas [NSCLC]; and 24 small cell lung carcinomas [SCLC]) and 269 lung normal epithelium and preneoplastic lesions, including hyperplasias, squamous metaplasias, dysplasias, and atypical adenomatous hyperplasias. RESULTS. High levels of nuclear immunohistochemical expression of NF-kappa B p65 were detected in the lung cancers, with significantly higher levels in SCLCs compared with NSCLCs (P <.0001). In adenocarcinomas the NF-kappa B p65 expression level was significantly higher in advanced TNM stages (III-IV) than in earlier stages (I-II) (P <.0001), and when NF-kappa B p65 is dichotomized using 50% as the cutoff point (high vs low), a higher NF-kappa B p65 expression level was detected in tumors having either K-RAS (P =.02) or EGFR (P =.009) mutations compared with wildtype tumors. A relatively high level of nuclear NF-kappa B p65 expression was detected in normal and mildly abnormal epithelium, and a progression with increasing histology severity was detected in preneoplastic lesions. CONCLUSIONS. NF-kappa B p65 nuclear expression is an early and frequent phenomenon in the pathogenesis of lung cancer. The findings indicate that NF-kappa B activation plays an important role in lung cancer pathogenesis and is a suitable target for the development of new lung cancer therapies and chemoprevention strategies.