Increased expression of β‐catenin predicts better prognosis in nonsmall cell lung carcinomas

Abstract

BACKGROUNDβ‐Catenin has been shown to function as a Wnt signaling molecule to stimulate cyclin D1 expression and cell growth in several kinds of tumors.METHODSThe authors immunohistochemically examined specimens of 217 surgically resected primary nonsmall cell lung carcinomas (NSCLCs) for β‐catenin expression and classified them semiquantitatively into three categories, including those with high, moderate, and low scores of expression.RESULTSHigh, moderate, and low scores of expression were found in 37 (17.1%), 145 (66.8%), and 35 (16.1%) tumors, respectively. β‐Catenin expression was not correlated with cyclin D1 expression, but was positively correlated with the Ki‐67 cell growth fraction (P = 0.04). The direct sequencing analysis for the β‐catenin gene mutation of 13 specimens of 217 tumors for the current study revealed no mutations. The relation between survival and β‐catenin expression was evaluated in 148 potentially curatively resected tumors with pathologic Stages I–IIIA. A trend toward better survival was found in patients with tumors having higher scores. In multivariate analysis, high β‐catenin expression was a significant and independent favorable prognostic factor (hazards ratio, 0.31; P = 0.007) as was pathologic stage. Analyzed by cell type, in nonsquamous cell carcinomas, patients with tumors having high scores survived a significantly longer time than those with tumors having moderate or low scores (5‐year survival rates, 84%, 55%, and 32%, respectively; P = 0.02), and high β‐catenin expression tended to be a favorable prognostic factor (hazards ratio, 0.32; P = 0.052).CONCLUSIONSThese results indicate that, in NSCLCs, increased expression of β‐catenin can predict favorable prognosis of patients with resected tumors, suggesting that accumulation of β‐catenin has no or little oncogenic effect via activation of the Wnt pathway, unlike in colon carcinomas or hepatomas. Cancer 2002;94:752–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10213

Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression

“…In mesothelioma, it appears to induce tumorigenicity via a canonical Wnt signaling pathway. Wnt signaling to date has been reported to be occasionally involved in lung carcinogenesis (Sunaga et al, 2001;Ueda et al, 2001;Hommura et al, 2002;Winn et al, 2002). Interestingly, a recent report identified Wnt signaling in lung cancer cell lines that corroborated active canonical Wnt signaling (Winn et al, 2002).…”

p53 mutation as a source of aberrant β-catenin accumulation in cancer cells

“…Cytoplasmic and/or nuclear accumulation of bcatenin is a highly frequent event affecting various cancers including colorectal, lung, breast, cervix cancers, melanoma, HCC and hepatoblastoma (Candidus et al, 1996;Rimm et al, 1999;Chung, 2000;Johnsson et al, 2000;Lin et al, 2000;Park et al, 2001;Shinohara et al, 2001;Ueda et al, 2001;Hommura et al, 2002;Inagawa et al, 2002). In colorectal cancers, b-catenin accumulation is often associated with mutational inactivation of APC gene, which affects almost 80% of these tumors .…”

“…Thus, it is estimated that between 35 and 80% of HCCs, the aberrant b-catenin accumulation is not associated with a mutation affecting b-catenin, Axin1 or APC gene. Aberrant accumulation of bcatenin protein without associated mutations on bcatenin, APC or Axin1 gene is not limited to HCC, since mutations affecting these genes are absent or exceptional in several other common malignancies such as cancers of the breast, lung and cervix, and melanomas (Candidus et al, 1996;Rimm et al, 1999;Lin et al, 2000;Ueda et al, 2001;Shinohara et al, 2001;Hommura et al, 2002). Thus, in many tumors, aberrant accumulation of b-catenin cannot be linked to a known mutation affecting wnt pathway, raising the possibility that mutations affecting the genes involved in other pathways may also contribute to aberrant accumulation of b-catenin in cancer cells.…”

Prognostic significance of β-catenin expression in patients with non-small cell lung cancer: A meta-analysis

“…Additionally, one article (33) provided information about adenocarcinoma and squamous cell carcinoma, which we processed independently as two studies in the meta-analysis. Eventually, twelve literatures containing thirteen studies that met the inclusion criteria were selected (17,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43).…”

“…Nine studies were excluded by scrutinizing the entire paper. Of those excluded studies, five had insufficient data (22,(25)(26)(27)(28) and one analyzed the relationship between twelve studies (17,(35)(36)(37)(38)43) and calculated from available data in the other three original literatures (33,39,40). For the remaining three studies (34,41,42), HR and 95% CI were extrapolated from Kaplan-Meier curves.…”