Nek2和β-连接素在乳腺浸润性导管癌中的表达和意义

Expressions and significances of Nek2 and β-catenin in breast invasive ductal carcinoma

目的 探讨中心体相关调节因子Nek2和β-连接素（β-cat）在人乳腺浸润性导管癌（IDC）和IDC伴发的导管内癌（DCIS）中的表达及其意义.方法 采用免疫组织化学方法（IHC）检测186例IDC、伴发的75例DCIS和80例癌旁正常组织及40例乳腺纤维腺瘤中Nek2和β-cat蛋白的表达定位及表达水平,并与其他多个临床病理参数进行比较分析.结果 IDC中不同组织学分级（Х^2=8.756;P〈0.05）、不同肿瘤大小（Х^2=6.518;P〈0.05）间Nek2细胞质表达不同,在其他指标分组间表达差异无统计学意义（P〉0.05）;Nek2细胞核表达在IDC中有32例（32/186）,在伴发的DCIS中有15例（15/75）;IDC中不同组织学分级（Х^2=45.493;P〈0.01）、TNM分期（Х^2=9.510;P〈0.01）、淋巴结转移（Z=-2.035;P〈0.05）、雌激素受体（ER）表达（Z=-3.004;P〈0.01）组间[β-cat细胞膜表达有差异,在其他临床病理参数组间差异无统计学意义（P〉0.05）;β-cat细胞质表达在不同TNM分期间差异有统计学意义（Х^2=8.194;P〈0.05）,在其他参数组间差异无统计学意义（P〉0.05）;伴发的75例DCIS中Nek2和β-cat表达在各病理学参数组间差异均无统计学意义（P〉0.05）,Nek2细胞质表达与β-eat细胞质表达正相关（r=0.226,P〈0.05）.IDC中Nek2细胞质表达与β-cat细胞质表达正相关（r=0.368,P〈0.01）.此外,在75例伴发DCIS的病例中,β-cat细胞膜表达率在DCIS中比IDC中要高（Z=-3.804,P〈0.01）.癌旁正常组织和纤维腺瘤中Nek2细胞质和细胞核均为低表达或阴性,β-cat细胞膜均为高表达而细胞质均为低表达.结论 研究中心体调节因子Nek2和β-cat的表达可能成为探讨乳腺浸润性导管癌发生发展机制的途径.

Objective To investigate the expression and significance of NIMA related kinases 2 （ Nek2） and β-catenin （β-cat） in breast invasive ductal carcinoma （IDC） and concomitant ductal carcinoma in situ （DCIS）. The roles of Nek2 and β-acat in the development and progression of breast cancer were explored. Methods The protein expression of Nek2 and β-cat in the tissues from 186 patients with IDC, 75 concomitant DCIS, 80 normal tissue adjacent to carcinoma and 40 fibroadenoma of breast was detected by using immunohistochemistry. Their relationship between clinicopathologic parameters was analyzed. Results There were correlations between the Nek2 expression in cytoplasm and grade（Х^2=8. 756;P〈0.05） as well as tumor size （Х^2=6. 518;P〈0.05） in IDC. The positive expression of Nek2 in nuclei was 32/186 and 15/75 in IDC and DCIS, respectively. There were correlations between the β-cat expression on the cytomembrane and grade （Х^2=45.493;P〈0. 01） , TNM stage （Х^2=9. 510;P〈0. 01）, node status （Z=-2.035;P〈0. 05） and estrogen receptor （ER） status （Z=-3. 004;P〈0. 01）. The β-cat expression on the cytoplasm was related with TNM stage （Х^2=8. 194;P〈0. 05）. The expression of Nek2 and β-cat had no correlation with clinicopathologic parameters in concomitant DCIS （P〉0. 05）, the Nek2 expression in cytoplasm had a correlation with the β-cat expression in cytoplasm （r=0. 226,P〈0.05） in concomitant DCIS, and the same relationship could also be seen in IDC （r=0. 368,P〈0.01）. There was significant difference in the β-cat expression on the cytomembrane between IDC and concomitant DCIS （Z=-3. 804,P〈0. 01）. In the normal tissue adjacent to carcinoma and fibroadenoma, the Nek2 expression in cytoplasm and nuclei Was low or negative;the β-cat expression on the cytomembrane was high but that Was low in cytoplasm.Conclusion Centrosome regulatory factor Nek2 and β-cat can support a new way to explore the mechanisms of breast tumorigrenesis.And they may become a new antitumor drug target in the future.