Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear β-catenin in cerebral metastasis of lung adenocarcinomas

作者: A. Bleckmann , L. Siam , F. Klemm , E. Rietkötter , Chr. Wegner

DOI: 10.1007/S10585-012-9552-7

关键词: AdenocarcinomaCancer researchSurvival rateWnt signaling pathwayCateninLung cancerCell nucleusImmunohistochemistryPathologyBiologyProliferation index

摘要: An essential function of the transcription factors LEF1/TCF4 in cerebral metastases lung adenocarcinomas has been described mouse models, suggesting a WNT/β-catenin effect as potential mechanism. Their role humans is still unclear, thus we analyzed LEF1, TCF4, β-catenin, and early stage prognostic markers 25 adenocarcinoma brain using immunohistochemistry (IHC). IHC revealed nuclear TCF4 all samples, whereas only 36 % depicted LEF1 β-catenin signals. Samples with well high (++++) expression were associated shorter survival (p = 0.01, HR = 6.68), while had no significant impact on prognosis did not significantly correlate LEF1. High proliferation index Ki67 was late-stage disease (p = 0.03, HR 3.27). Additionally, generated an AXIN2 signature, latter representative activity, following bioinformatics approach gene dataset adenocarcinoma. To analyze relevance primary adenocarcinomas, applied both signatures to microarray 58 adenocarcinomas. Only signature able separate clusters HR = 0.32). These displayed diverging enrichment patterns cell cycle pathway. In conclusion, our data show that LEF1/TCF4, but have cerebrally metastasized human contrast previous vivo findings, these results indicate act independently this setting.

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