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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 overexpression of p21-activated kinase 1 (PAK1) gene in epithelial ovarian tumors and its mechanism and significance. Methods Immunohistochemistry, fluorescence in situ hybridization and terminal deoxynucleotidyl transferase-mediated nick end labeling were used to detect PAK1 gene expression in 30 ovarian adenomas, 20 ovarian borderline tumors and 80 ovarian tissues Cancer expression, expansion and apoptosis. Results In immunohistochemically validated cases, PAK1 protein overexpression was found in 7 cases (25.9%) of ovarian benign adenomas, 7 cases (36.8%) of borderline tumors and 53 cases (68.8%) of ovarian carcinomas , And the overexpression of PAK1 was negatively correlated with the apoptosis index of ovarian tumors (P = 0.002). In addition, overexpression of PAK1 protein was found in 87.1% (27/31) of poorly differentiated ovarian cancers (Silverberg G3), which was significantly higher than that of G1 to G2 ovarian cancers (26/46, 56.5 %; P = 0.01). Fluorescence in situ hybridization showed that only 2 cases (4.7%) of ovarian cancer PAK1 gene amplification, borderline ovarian tumors and benign adenomas did not observe PAK1 gene amplification. Conclusion PAK1 protein overexpression may play an important role in the development of ovarian epithelial tumors and is closely related to the malignant histological phenotype of ovarian cancer. In the regulation of PAK1 protein expression in ovarian tumors, other regulatory mechanisms besides gene amplification May play a more crucial role.