乳腺癌组织INPP4B与β-catenin表达临床意义

Expression and significance of INPP4B and β-catenin in breast cancer

目的癌细胞转移是造成乳腺癌患者死亡的最主要原因之一,Ⅱ型多磷酸肌醇4-磷酸酶(inositol polyphosphate 4-phosphatasetypeⅡ,INPP4B)是一种新发现的、具有抑癌作用的脂质磷酸酶,β-catenin是Wnt信号通路的关键因子,许多人类恶性肿瘤的发生被认为与异常激活的Wnt/β-catenin通路相关。本研究分析INPP4B和β-catenin蛋白在乳腺癌组织中的表达,并探讨其临床意义。方法收集2014-01-10-2015-12-12沧州市中心医院病理科乳腺癌组织标本248例和同期乳腺良性病变组织标本25例,通过免疫组化法检测INPP4B和β-catenin蛋白,分析INPP4B蛋白表达与临床病理特征和β-catenin蛋白异位表达的关系。结果248例乳腺癌组织中INPP4B阳性表达率为29.45%(73/248),低于正常乳腺组织84.00%(208/248)的阳性表达率,差异有统计学意义,P<0.05;β-catenin蛋白在乳腺癌组织中的异位表达率为69.35%(172/248),高于正常乳腺组织的异位表达,差异有统计学意义,P<0.05;INPP4B蛋白阳性表达率与患者年龄(t=0.430,P=0.573)、肿瘤直径(t=1.548,P=0.216)、ER(t=0.015,P=0.507)、PR(t=0.687,P=0.486)和HER2(t=0.531,P=0.481)等无关联,与乳腺癌TNM分期(t=8.364,P=0.029)以及组织学分级(t=8.107,P=0.018)呈正相关,与β-catenin蛋白异位表达呈负相关(t=-0.908,P=0.000 8);INPP4B和Ecadherin蛋白随乳腺癌TNM分期升高而降低,而Wnt1和Ki-67蛋白则随乳腺癌TNM分期升高而升高。结论 INPP4B蛋白在乳腺癌组织中表达下调,而β-catenin在乳腺癌组织中异位表达上调,两者表达呈负相关,提示INPP4B可能通过wnt/β-catenin信号通路参与乳腺癌的发生发展。

OBJECTIVE Metastasis of cancer cells is one of the leading causes of death in breast cancer patients. IN PP4B is a newly discovered lipid phosphatase with tumor suppressor activity,and β-catenin is a key factor in the Wnt sig naling pathway. Many human malignancies are thought to be associated with abnormally activated Wnt/β-catenin path ways. In this paper,we studied the expression and significance of INPP4B and β-catenin in breast cancer. METHODS To tally 248 cases of breast cancer tissue samples and 25 cases of benign breast lesions were collected in Cangzhou Central Hospital collection pathology from 2014-01-10 to 2015 12-12. The expression of INPP4B and β-catenin in 2.48 cases of breast cancer and 25 cases of normal breast tissue were detected by Immunohistochemistry,and the relationship between INPP4B protein expression and clinicopathological features and t3 catenin protein ectopic expression were analyzed. RE- SULTS The positive expression rate of INPP4B in 208 cases of breast cancer was 29.45G（73/248）,which was signifi cantly lower than that in normal breast tissue（84. 00%, P%70.05）. The ectopic expression rate of 13 catenin protein in breast cancer was 69.35% （172/248）,which was significantly higher than that in normal breast tissue（P〈0.05）. The positive expression rate of INPP4B protein was not correlated with age（t 0. 430,P 0. 573） ,tumor diameter（t 1. 548, P=O. 216）,ER（t=O. O15,P=O. 507）,PR（t=O. 687,P=0.486） andHER2（g 0.531,P=0.481. Lymphnodemctastasis （t=8.364,P=0.029） and histological grade（t-8. 107,P 0.018） were significantly correlated with the ectopic expres sion of β-catenin protein（t= -0. 908 ,P 0. 000 8）. INPP4B and Ecadherin were decreased with the increase of TNM staging of breast cancer,while Wntl and Ki-67 protein was increased with the TNM staging of breast cancer. CONCLUSIONS IN PP4B protein is down regulated in breast cancer tissues,and the ectopic expression of β-catenin in breast is upregulated.The negative correlation between INPP4B and β-catenin prompt that INPP4B may be involved in the development of breast cancer through the wnt/β-catenin signaling pathway.