卵巢上皮性癌nm23H1基因遗传不稳定性与临床病理特性的关系  

Correlation of Genetic Instability of nm23H1 Gene to Clinicopathologic Features of Epithelial Ovarian Carcinoma

作　　者：杨月琴[1] 李继承[1] 

机构地区：[1]浙江大学细胞生物学研究所,浙江杭州310031

出　　处：《癌症》2006年第6期713-717,共5页Chinese Journal of Cancer

基　　金：浙江省分析测试基金资助(No.03149)~~

摘　　要：背景与目的:基因的遗传不稳定性,包括微卫星不稳定(microsatelliteinstablility,MSI)和杂合性缺失(lossofheterozygosity,LOH),是导致抑癌基因功能失调,引起肿瘤发生的重要因素。本实验研究中国人17号染色体D17S396位点MSI和LOH对卵巢上皮性癌nm23H1蛋白表达的影响,阐明nm23H1基因遗传不稳定性与卵巢上皮性癌临床病理特性的关系,为揭示nm23H1基因作用机制和肿瘤转移机制提供实验依据。方法:采用PCR-单链构象多态性(PCR-SSCP)和常规银染检测25例卵巢上皮性癌及相应的非癌组织D17S396位点的MS和LOH,采用EnVision免疫组织化学和Leica-Qwin计算机图像分析检测nm23H1蛋白表达。结果:25例卵巢上皮性癌中,D17S396位点MSI、LOH检出率和nm23H1蛋白阳性率分别为16.00%、24.00%和56.00%。LOH发生率在淋巴转移组(66.67%)高于无淋巴转移组(10.53%,P<0.01),在FIGOⅢ+Ⅳ期(50.00%)高于Ⅰ+Ⅱ期(11.76%,P<0.05)。nm23H1蛋白阳性率在淋巴转移组(16.67%)低于无淋巴转移组(68.42%,P<0.05);FIGOⅢ+Ⅳ期(25.00%)低于Ⅰ+Ⅱ期(70.59%,P<0.05)。计算机图像定量分析显示,在各临床病理参数影响下,nm23H1蛋白的表达强度没有差异。此外,LOH阳性组中nm23H1蛋白阳性率为0.00%,显著低于LOH阴性组的73.68%(P<0.01)。结论:LOH的发生可作为卵巢组织恶变的判断指标。nm23H1基因的MSI和LOH,通过相互独立的途径调控卵巢上皮癌的发生和转移,后者可抑制卵巢上皮性癌局部nm23H1的表达,并与卵巢上皮癌高淋巴结转移、预后差有关。BACKGROUND ＆ OBJECTIVE. Genetic instability, including microsatellite instability （MSI） and loss of heterozygosity （LOH）, is the main reason for anti-oncogenes function maladjustment, and tumorigenesis. This research was to explore the correlation of genetic instability of nm23H1 gene to clinicopathologic features of epithelial ovarian carcinoma, and provide experimental basis for revealing the mechanism of nm23H1 gene function and tumor metastasis. METHODS. MSI and LOH of locus D17S396 in 25 specimens of epithelial ovarian carcinoma and relevant pericancerous tissues were detected by polymerase chain reaction-single strand conformation polymorphism （PCR-SSCP） with ordinary silver staining. EnVision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1 protein. RESULTS. The detection rates of MSI and LOH of locus D17S396 in the 25 specimens of epithelial ovarian carcinoma were 16.00% and 24.00%, and the positive rate of nm23H1 protein was 56.00%. The frequency of LOH was significantly higher in the cases with lymph node metastasis than in those without metastasis （66.67% vs. 10.53%, P〈0.01）, and was significantly higher in the cases at FIGO stage Ⅲ -Ⅳ than in those at stage Ⅰ - Ⅱ （50.00% vs. 11.76%, P〈0.05）. The positive rate of nm23H1 protein was significantly lower in the cases with lymph node metastasis than in those without lymph node metastasis （16.67% vs. 68.42%, P〈0.05）, and was significantly lower in the cases at FIGO stage Ⅲ -Ⅳ than in those at stage Ⅰ - Ⅱ （25.00% vs. 70.59%, P〈0.05）. The expression intensity of nm23H1 protein had no correlation to clinicopathologic factors of epithelial ovarian carcinoma when analyzed by computer imaging techniques. The positive rate of nm23H1 protein was significantly lower in the cases with LOH of locus D17S396 than in those without LOH of locus D17S396 （0.00% vs. 73.68%, P〈0.01）. CONCLUSIONS. The occurrence of LOH may be a molecular marker for the cancer

关 键 词：卵巢肿瘤/遗传学 NM23H1基因 MSI LOH 遗传不稳定性 淋巴结转移 预后 

分 类 号：R737.31[医药卫生—肿瘤] R730.231[医药卫生—临床医学]