Wnt信号通路在乳腺癌中的作用

Significance of Wnt signaling in breast carcinoma

目的探讨乳腺癌中Wnt信号通路关键因子β-catenin的突变和表达及靶基因cyclinD1、c-myc的表达及意义。方法应用免疫组化SP法检测119例乳腺癌,72例乳腺增生症和40例正常乳腺组织中β-catenin、cyclinD1、c-myc的表达,并分析其与乳腺癌临床病理特征的关系。应用PCR和基因测序的方法检测44例乳腺癌β-catenin外显子3的突变情况,同时应用免疫组化SP法检测其β-catenin的表达。结果40例正常乳腺组织中β-catenin在细胞膜中强表达,cyclinD1及c-myc阴性表达。乳腺癌β-catenin异常表达率明显高于乳腺增生症,组间比较差异有显著性(78.15%vs44.44%,P<0.01),乳腺癌cyclinD1、c-myc阳性表达率高于乳腺增生症(57.98%vs33.33%;56.30%vs27.78%,均P<0.01)。β-catenin异常表达、cyclinD1的过表达与淋巴结转移相关,c-myc的过表达与肿瘤大小和淋巴结转移相关。β-catenin的异常表达与cyclinD1的表达相关,而与c-myc的表达无关。44例乳腺癌组织中未检测到β-catenin基因外显子3的突变,β-catenin的异常表达率为77.30%。结论β-catenin异常表达是乳腺癌发生发展过程中的重要因子,这个过程可能是通过激活cyclinD1实现的。β-catenin异常表达和cyclinD1、c-myc过表达可作为评估乳腺癌转移预后、指导治疗的指标。乳腺癌组织中细胞内β-catenin异常积聚不是由β-catenin基因突变所致,可能存在其他机制。

Objective To investigate the mutation and expression of β-catenin and the expression of cyclinD1, c-myc in breast carcino- ma. Methods The expression of β-catenin, cyclinD1 ,c-myc was detected using immunohistochemistry in 119 cases of breast carcino- ma tissues ,72 cases of breast cystic hyperplasia tissues and 40 cases of normal breast tissues. The relationships of β-catenin, cyclinD1, c-myc expression with the clinicopathological features of breast carcinomas were analyzed. Gene mutation of β-catenin （ exon 3 ） in 44 cases of breast carcinoma was analyzed by polymerase chain reaction （PCR）and direct sequencing, and the expression of β-catenin was detected using immunohistochemistry. Results In 40 cases of normal breast tissues, β-catenin protein was expressed strongly in the membrane of epithelial cells,but the expression of cyclinD1, c-myc was negative. The abnormal rate of β-catenin was much higher in breast carcinomas than that in breast cystic hyperplasia（78.15% vs 44.44%, P 〈 0.01 ）. The overexpression of cyclinD1, c-myc was significantly higher in breast carcinomas than that in breast cystic hyperplasia（ 57. 98% vs 33.33%, P 〈 0.01 ;56.30% vs 27.78%, P 〈0.01）. The abnormal expression of β-catenin and the overexpression of cyclinD1 were associated with the lymph node metastasis （P = 0. 031 ,P = 0.003 ）. The overexpression of c-myc was associated with the size and the lymph node metastasis （P = 0. 041, P = 0.041 ）. The abnormal expression of β-catenin was significantly related to the overexpression of cyclinD1 （ P = 0. 006）, but not to the overexpression of c-myc （P = 0.775 ）. Mutation of [3-catenin gene was not detected in 44 cases of breast carcinoma, while the abnormal rate of [3-catenin was 77.30%. Conclusion The abnormal expression of β-catenin could play a key role in the carcinogenesis and progression of human breast carcinoma by up-regulating the expression of cyclinD1.β-catenin abnormal expression and the overexpres- sion of cyclinD1, c-myc could be considered as the useful makers for determining metastasis and prognosis of human breast carcinoma and guiding the treatment. β-catenin abnormal expression is not caused by β-catenin gene mutation, which needs a further study.