Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions.
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.
Tang
Ximing
X
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Liu
Diane
D
Shishodia
Shishir
S
Ozburn
Natalie
N
Behrens
Carmen
C
Lee
J Jack
JJ
Hong
Waun Ki
WK
Aggarwal
Bharat B
BB
Wistuba
Ignacio I
II
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018773:Genes, erbB-1; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051996:Transcription Factor RelA / Q000096:biosynthesis*
D051996:Transcription Factor RelA