SOX7、β-catenin和cyclin D1蛋白在浸润性乳腺癌组织中的表达及临床意义

Research of expression and clinical significance of SOX7, β-catenin and cyclin D1 protein in invasive breast cancer

目的 观察SOX7、β-catenin和cyclin D1蛋白在浸润性乳腺癌与乳腺良性增生病组织中的表达,探讨它们与浸润性乳腺癌临床病理学特征之间的关系,为浸润性乳腺癌的治疗、预后提供有价值的生物学标志.方法 应用免疫组化SP法分别检测50例浸润性乳腺癌与30例乳腺良性增生病中SOX7、β-cate-nin和cyclin D1蛋白的表达情况,分析SOX7、β-catenin和cyclin D1蛋白的表达与浸润性乳腺癌患者的发病年龄、肿瘤大小、腋窝淋巴结转移、组织学分级、病理学分期（pTNM）、雌激素受体（ER）、孕激素受体（PR）、人类表皮生长因子受体2（Her-2）和危险度分组之间的关系.结果 在50例浸润性乳腺癌组织中,SOX7和cyclin D1蛋白的阳性表达率分别为42％（21/50）和70％（35/50）,β-catenin蛋白的异常表达率为70％（35/50）.在浸润性乳腺癌中,SOX7蛋白的阳性率明显低于乳腺良性增生病的70％ （21/30） （P =0.021＜0.05）,两组间差异有统计学意义；β-catenin蛋白的异常表达率和cyclin D1蛋白的阳性表达率均高于乳腺良性增生病的43.3％ （13/30） （P =0.033 ＜0.05）和20％ （6/30） （P =0.000＜ 0.001）,两组间差异均有统计学意义.在50例浸润性乳腺癌中,SOX7和β-catenin蛋白同时阳性表达12例,同时阴性表达5例；SOX7和cyclinD1蛋白同时阳性表达11例,同时阴性表达5例；β-catenin和cyclinD1蛋白同时阳性表达28例,同时阴性表达8例.经Spearman相关分析,SOX7蛋白的阳性表达分别与p-catenin的异常表达和cyclin D1的阳性表达呈负相关关系（r=-0.282,P=0.046 ＜0.05;r =-0.327,P =0.020 ＜0.05）,β-catcnin的异常表达与cyclin D1的阳性表达呈正相关关系（r=0.333,P=0.018 ＜0.05）.在浸润性乳腺癌中,SOX7蛋白的表达在发病年龄、腋窝淋巴结转移、组织学分级、pTNM分期、ER、PR、Her-2和危险度分组间差异有统计学意义（P＜0.05）,而在肿瘤直径分组间比较差异无统计学意义（P ＞0.05）；β-catenin蛋白的异常表达和cyclin D1蛋白的阳性表达在肿瘤直径、腋窝淋巴结转移和pTNM分期分组间差异有统计学意义（P＜0.05）,而在发病年龄、组织学分级、ER、PR、Her-2和危险度分组间比较差异无统计学意义（P＞0.05）.结论 SOX7、β-cate-nin和cyclinD1蛋白在大多数浸润性乳腺癌组织中表达异常,且三者在浸润性乳腺癌发生、发展过程中可能通过同一通路发挥调节作用.SOX7、β-catenin和cyclin D1蛋白的表达与浸润性乳腺癌的临床病理学特征之间存在一定的相关性,检测三者的表达情况可成为临床上判断浸润性乳腺癌的恶性程度及预后的重要参考指标.

Objective This study aimed to investigate the expression of SOX7,β-catenin and cyclin D1 in invasive breast cancer and hyperplastic disease of the breast,and explore their relationship with clinical pathology charactersis in invasive breast cancer in order to provide valuable biomarkers for the treatment and prognosis.Methods The expression of SOX7,β-catenin and cyclin D1 was neasured in 50 invasive breast cancer tissues and 30 hyperplastic disease of the breast by immunohistochemical SP method.The correlations of SOX7,β-catenin and cyclin D1 in invasive breast cancer to clinicopathologic features were analyzed,such as age,size of tumor,axillary lymph node metastasis,histological grade,pTNM stage,ER,PR,Her-2 expression and the risk.Results Immunohistochemical results showed that the positive rates of SOX7 and cyclin D1 in invasive breast cancer were 42％ （21/50）and 70％ （35/50）,and the abnormal expression rates of β-catenin in invasive breast cancer was 70％ （35/50）.The positive rates of SOX7 in invasive breast cancer was significantly lower than that in hyperplastic disease of the breast 70％ （21/30）.The expression of SOX7 had difference between two groups （P =0.021 ＜0.05）.The abnormal expression rates of β-catenin and the positive rates of cyclin D1 in invasive breast cancer wcre significantly higher than that in hyperplastic disease of the breast 43.3％ （13/30） （P =0.033 ＜ 0.05） and 20％ （6/30） （P =0.000 ＜ 0.001）.The expression of β-catenin and cyclin D1 had difference between two groups.In invasive breast cancer,SOX7 and β-catenin protein expression in 12 cases,while negative expression in 5 cases; SOX7 and cyclin D1 protein positive expression in H 1 cases,while negative expression in 5 cases; β-catenin and cyclin D1 protein positive expression iu 28 cases,while negative expression in 8 cases.Results of the analysis by Spearman showed that in invasive breast cancer the SOX7 protein expression was negatively correlated with the abnormal expression of β-catenin protein and the expression of cyclin D1 protein（r =-0.282,P =0.046 ＜ 0.05 ;r =-0.327,P =0.020 ＜ 0.05）while the abnormal expression of β-catenin protein was positively correlated with the expression of eyclin D1 protein（r =0.333,P =0.018 ＜ 0.05）.In invasive breast cancer the expression of SOX7 protein was correlated with age,axillary lymph node metastasis,histological grade,pTNM stage,ER,PR,Her-2 expression and the risk（P ＜0.05）,but with no correlation with size of tumor （P ＞ 0.05）.However,the abnoral expression of β-catenin and the positive expression of cyclin D1 in invasive breast cancer were correlated with size of tumor,axillary lymph node metastasis and pTNM stage（P ＜ 0.05）,but with no correlation with age,histological grade,ER,PR,Her-2 and the risk（P ＞0.05）.Conclusions SOX7.β-catenin and cyclin D1 are frequently abnormality-regulated in invasive breast cancer tissues,and the three protein may play a regulatory role through the same pathway in the development and progression of invasive breast cancer.SOX7,β-catenin and cyclin D1,s abnormal expression in invasive breast cancer correlate with the clinical pathology charactersis,and the three protein may be valuable marker for assessing the prognosis for invasive breast cancer.