背景与目的 β-连环素(β-catenin)和T细胞因子4(TCF-4)表达与非小细胞肺癌(NSCLC)临床病理因素相关,本研究的目的是分析NSCLC中β-连环素与TCF-4的关系和意义。方法 应用免疫组化方法观察NSCLC中β-连环素表达情况;应用免疫荧光、免疫共沉淀、原位杂交等方法分析NSCLC中β-连环素异常定位、蓄积及与TCF-4的关系。结果 NSCLC中β-catenin的蛋白和mRNA水平明显高于癌旁正常肺组织,β-连环素在NSCLC肿瘤细胞胞浆和(或)胞核异常表达率为78.74%(100/127),其中核表达率为37.01%(47/127)。β-连环素异常表达与分化程度(P=0.0008)和淋巴结转移(P=0.017)相关。TCF-4在86.67%(52/60)的肿瘤细胞核和(或)浆表达,中、低分化肺癌组织的TCF-4表达强度显著高于高分化癌组织。免疫共沉淀检测发现β-连环素和TCF-4核内共同表达的病例中有76.47%(13/17)存在β-连环素/TCF-4复合体,其中核内61.54%,浆内38.46%。结论 β-连环素蛋白和 mRNA的异常表达与NSCLC的恶性表型有关。TCF-4的表达与肺癌的低分化程度相关,β-连环素/TCF-4复合体在NSCLC中较普遍存在。
Background and objective It has been known that the expressions of β-catenin and T cell factor 4 (TCF-4) were associated with clinicopathological parameters in non-small cell lung cancer (NSCLC). The objective of this study is to explore the relationship between expressions of β-catenin and TCF-4 in NSCLC. Methods The expression of β-catenin was detected with immunohistochemistry in 100 lung cancer samples; the relationship between abnormal located and preserved β-catenin with TCF-4 was investigated by immunofluorescence, co-immunoprecipitation and hybridization in situ. Results The levels of protein and mRNA were both significantly higher in NSCLC than in corresponding normal lung tissues. Aberrant cytoplasmic and/or nuclear expression of β-catenin were 78. 74% (100/127) while aberrant nuclear expression was 37.01% (47/127). Aberrant nuclear β-catenin was significantly associated with differentiation (P=0. 0008) and lymphatic metastasis (P= 0. 017). Positive TCF-4 expression (86.67 %, 52/60) was normally seen in nucleus and cytoplasm of cancer cells. The intensity of TCF-4 expression was significantly higher in moderately and poorly differentiated lung cancers than that in well differentiated ones. In total 17 cases of β-catenin (+) and TCF-4 (+) patients, 13 cases were detected with the β-catenin/TCF-4 complex, 61.54% in nucleus and 38.46% in cytoplasm. Conclusion The abnormal mRNA and protein expressions of β-catenin are associated with malignant phenotype in NSCLC. TCF-4 expression is associated with poor differentiation in lung cancers. The β-catenin/TCF-4 complex exists widely in NSCLC.