Background: Nuclear factor-kappaB (NF-kappaB), a key transcription factor thought to play a major role in carcinogenesis, regulates many important signaling pathways involved in tumor promotion. Although NF-kappaB can be activated in lung cancer cell lines by tobacco exposure, there have been no studies of the expression of NF-kappaB in lung cancer pathogenesis.
Methods: The immunohistochemical expression of NF-kappaB 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-kappaB p65 were detected in the lung cancers, with significantly higher levels in SCLCs compared with NSCLCs (P<.0001). In adenocarcinomas the NF-kappaB p65 expression level was significantly higher in advanced TNM stages (III-IV) than in earlier stages (I-II) (P<.0001), and when NF-kappaB p65 is dichotomized using 50% as the cutoff point (high vs low), a higher NF-kappaB 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-kappaB p65 expression was detected in normal and mildly abnormal epithelium, and a progression with increasing histology severity was detected in preneoplastic lesions.
Conclusions: NF-kappaB p65 nuclear expression is an early and frequent phenomenon in the pathogenesis of lung cancer. The findings indicate that NF-kappaB 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.
(c) 2006 American Cancer Society.