摘要
目的探讨p21-激活激酶1(PAK1)基因在卵巢上皮性肿瘤中的过度表达及其机制和意义。方法运用免疫组化、荧光原位杂交和末端脱氧核苷酸转移酶介导缺口末端标记方法,结合组织芯片技术,检测PAK1基因在30例卵巢腺瘤、20例卵巢交界性肿瘤和80例卵巢癌中的表达、扩增及其细胞凋亡情况。结果在免疫组化有效检测的病例中,7例(25．9％)卵巢良性腺瘤、7例(36．8％)交界性肿瘤和53例(68.8％)卵巢癌出现PAK1蛋白的过度表达,而且PAK1蛋白过表达与卵巢肿瘤的细胞凋亡指数呈负相关(P=0．002)。此外,87．1％(27／31)的低分化卵巢癌(Silverberg G3级)出现PAK1蛋白的过度表达,其过表达率显著高于G1～G2级的卵巢癌(26／46,56．5％;P= 0．01)。荧光原位杂交结果显示,只有2例(4．7％)卵巢癌出现PAK1基因扩增,卵巢交界性肿瘤和良性腺瘤均未观察到PAK1基因的扩增。结论PAK1蛋白过度表达可能在卵巢上皮性肿瘤的发生发展中起重要作用,而且与卵巢癌的恶性组织学表型密切相关;在卵巢肿瘤PAK1蛋白的表达调控中,基因扩增以外的其他调节机制可能起更为关键的作用。
Objective To investigate the significance and mechanisms of overexpression of p21- activated kinase 1 gene （PAK1） in epithelial ovarian neoplasms. Methods Immunohistochemistry, fluorescence in situ hybridization and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling methods were used to examine the protein expression and amplification of PAK1 and cell apoptosis in 30 benign ovarian adenomas, 20 borderline tumors and 80 ovarian carcinomas by tissue microarray. Results In immunohistochemistry study, overexpression of PAKI protein was observed in 7 （ 25. 9% ） informative benign ovarian adenomas, 7 （36. 8%） borderline tumors and 53 （68. 8%） ovarian carcinomas. A significant inverse correlation of PAK1 overexpression and cell apoptosis was observed in these epithelial ovarian neoplasm cohorts （ P = 0. 002 ）. In addition, 27/31 （ 87. 1% ） poorly differentiated （（;3） carcinomas showed overexpression of PAK1, the frequency was significantly higher than that in tumors of G1 G2 （26/46, 56.5% , P =0.01 ）. In fluorescence in situ hybridization study, only 2 （4.7%） informative ovarian carcinomas showed amplification of PAK1 gene. None of the borderline and benign ovarian tumors showed PAK1 amplification. Conclusion Overexpression of PAKI protein may be involved in the tumorigenesis of epithelial ovarian neoplasms and it is associated closely with the malignant histological phenotype of ovarian carcinomas. Mechanism other than gene amplification of PAK1 may play a more important role in the regulation of protein expression of PAK1 in ovarian tumors.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2006年第12期911-914,共4页
Chinese Journal of Oncology
基金
广东省科技计划项目资助项目(2005A30801001)
关键词
卵巢肿瘤
PAK1基因
免疫组织化学
荧光原位杂交
组织芯片
Ovarian neoplasm
PAK1 gene
Immunohistochemistry
Fluorescence in situ hybridization
Tissue microarray
