卵巢癌中EIF-5A2 基因表达与临床意义*

目的:探讨真核翻译起始因子5A2（EIF-5A2）基因在卵巢上皮性肿瘤中的表达及其临床意义。方法:运用免疫组化和荧光原位杂交方法，结合组织芯片技术，检测EIF-5A2 基因在50例卵巢腺瘤、50例卵巢交界性肿瘤和150 例卵巢癌中的表达，分析其与肿瘤临床病理学参数之间的相关性。结果:免疫组化检测结果，分别有6.4% 的卵巢良性腺瘤、28.3% 的交界性肿瘤和56.6% 的卵巢癌出现EIF-5A2 蛋白的过度表达。在卵巢癌中，EIF-5A2 蛋白表达与肿瘤的组织学Silverberg 氏分级和临床FIGO分期均有显著的相关性（P<0.05），其中70.0% 的高级别（G3 级）的卵巢癌出现EIF-5A2 蛋白的过度表达，明显高于G1/G2 级的卵巢癌（49.5%）；在FIGO分期中，65.6% 的临床晚期（Ⅲ/Ⅳ期）卵巢癌呈EIF-5A2 蛋白过度表达，明显高于Ⅰ/Ⅱ期的肿瘤（38.3%）。 另外，EIF-5A2 蛋白过度表达与卵巢癌细胞增殖（Ki-67的表达水平）显著正相关（P<0.01），大多数（72.8%）EIF-5A2 蛋白过度表达的卵巢癌中出现Ki-67蛋白高表达，而多数（66.1%）EIF-5A2 蛋白正常表达的卵巢癌则呈Ki-67蛋白低表达。荧光原位杂交结果显示，只有13.8% 的卵巢癌出现EIF-5A2 基因扩增；卵巢交界性肿瘤和良性腺瘤中均未观察到EIF-5A2 基因的扩增。结论:EIF-5A2 蛋白过度表达可能通过促进肿瘤细胞增殖的效应，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和浸润转移密切相关。 

Expression of EIF-5A2 Gene in Ovarian Carcinoma and Its Clinical Significance

Objective: To investigate the expression and amplification of eukaryotic translation initiation factor 5A2 (EIF-5A2) gene in epithelial tumor of the ovary and its clinical significance. Methods:Immunohistochemistry and fluores -cence in situ hybridization, in combination with tissue microarray, were used to examine the protein expression and amplifi-cation of EIF-5A2 in 50ovarian adenomas, 50borderline tumors of the ovary and 150 ovarian carcinomas to evaluate the potential associations between EIF-5A2 expression and patient's clinico-pathologic parameters in ovarian carcinoma co-horts. Results: In the immunohistochemical assay, over-expression of EIF- 5A2 protein occurred in 6.4% of benign ovarian adenomas, 28.3% borderline tumors and 56.6% ovarian carcinomas. In ovarian carcinomas, there was a significant correla-tion in EIF- 5A2 expression, Silverberg's grading and FIGO staging (P<0.05), in which the over-expression of EIF-5A2 was observed in70.0% of high-grade (G3) carcinomas, with the positive rate significantly higher than that in the G1/G2 carcino-mas (49.5%). This over-expression also occurred in 65.6% of the carcinomas with late clinical stages (FIGO stage III/IV), with a significantly higher positive rate compared to that in the tumors with FIGO stage I/II (38.3%). Furthermore, there was a significant positive correlation between EIF-5A2 over-expression and cell proliferation (the levels of Ki-67expression) in our ovarian carcinomas (P<0.01), in which higher expression of Ki- 67was found in the majority of carcinomas with over-ex-pression of EIF-5A2 (72.8%), while lower expression of Ki-67was seen in the majority of carcinomas with normal expression of EIF-5A2 (66.1%). It was shown by fluorescence in situ hybridization assay that amplification of EIF-5A2 gene was present in only 13.8% of the ovarian carcinomas. EIF-5A2 amplification was not observed in the borderline or the benign ovarian tumors. Conclusion:Over-expression of EIF-5A2 protein may possibly, at least in part, play an important role in the tumorigenesis of epithelial tumors of the ovary through its effect of promoting cell proliferation. Moreover, it is in close correlation with the malignant histological phenotype and/or invasive process of ovarian carcinomas.