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上皮性卵巢肿瘤中EZH2和PTEN蛋白的表达及意义
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摘要
目的:研究EZH2和PTEN蛋白在上皮性卵巢肿瘤组织中的表达,并探讨两种蛋白与上皮性卵巢癌临床病理特征的关系及它们之间的相关性。
     方法:选用(陕西)超英生物科技公司的卵巢肿瘤组织芯片(OV1005),包括正常卵巢组织20例、上皮性良性卵巢肿瘤18例、上皮性交界性卵巢肿瘤7例、上皮性卵巢癌55例。采用免疫组化方法检测EZH2和PTEN蛋白在卵巢肿瘤组织芯片中的表达。采用X2检验和Fisher确切概率法分析EZH2和PTEN蛋白在各卵巢肿瘤组织中的表达及与临床病理因素之间的关系;用Spearman等级相关分析两种蛋白的相关性。
     结果:1.EZH2蛋白在正常卵巢组织、良性卵巢肿瘤、交界性卵巢肿瘤及卵巢癌组织中的表达率分别为5%、33.3%、42.9%、67.3%,四组间差别有统计学意义(P<0.05)。在卵巢癌组织中, EZH2在Ⅰ-Ⅱ期中的表达(56.7%)低于Ⅲ-Ⅳ期中的表达(88.9%),在无淋巴结无转移组中的表达(56.8%)低于有转移组中的表达(100%),两组间差别均有统计学意义(P<0.05);随病理分级的升高,EZH2蛋白表达水平也增高,G1、G2、G3中EZH2阳性表达率分别为:42.9%、78.3%、90.9%,三组间差别有统计学意义(P<0.05);EZH2蛋白的表达水平在不同的年龄、病理类型中差异无显著性(P>0.05);
     2.PTEN在正常卵巢组织、良性卵巢肿瘤、交界性卵巢肿瘤及卵巢癌组织中的表达率分别为100%、66.7%、42.9%、38.2%,四组间差别有统计学意义(P<0.05)。在卵巢癌组织中,PTEN在Ⅰ-Ⅱ期中的表达(51.4%)高于Ⅲ-Ⅳ期中的表达(11.1%),在无淋巴结转移组中的表达(51.4%)高于有淋巴结转移组中的表达(0%),两组间差别均有统计学意义(P<0.05);随病理分级的升高,PTEN表达水平降低,G1、G2、G3中PTEN阳性表达率分别为:66.7%、21.7%、18.2%,三组间差别有统计学意义(P<0.05);PTEN蛋白的表达水平在不同的年龄、病理类型中差异无显著性(P>0.05)。
     3.在卵巢癌组织中,EZH2和PTEN蛋白表达存在负相关(rs=-0.425,P=0.001)。
     结论:1.EZH2蛋白在卵巢癌组织中高表达,且与临床期别晚、肿瘤分化差及有淋巴结转移密切相关,说明EZH2蛋白可能参与卵巢癌的发生、发展,同时预示该蛋白可能与卵巢癌侵袭转移有关。
     2.PTEN蛋白在卵巢癌组织中低表达,且与临床期别晚、肿瘤分化差及有淋巴结转移也相关,提示PTEN蛋白的缺失可能与卵巢癌的发生、发展有关,同时说明PTEN蛋白具有抑制卵巢癌肿瘤细胞侵袭转移的作用。
     3.EZH2和PTEN蛋白的表达呈显著负相关,推测PTEN可能通过对EZH2的抑制作用共同参与卵巢癌的发生发展,联合检测对于评价卵巢癌的恶性程度及转移更具有临床价值。
Objective:To investigate the expression of EZH2 and PTEN protein in ovarian tumor tissue, and to explore the relations to clinicopathologic characters of ovarian carcinoma and the relationship of themselves
     Methods:Ovarian cancer tissue microarray(OV1005) which was Choosed from chaoying biotechnology company, containing normal oarian tissue 20 cases, benign ovarian tumor 18 cases, border ovarian tumor 7 cases, ovarian carcinoma 55 cases. Then, to detect the expression of EZH2 and PTEN protein by immunohistochemical SP method. The correlations of EZH2 and PTEN with clinicopathological characters were analyzed by X2 test or Fisher'S exact test; their relationship by Spearman.
     Results:1. The expression of EZH2 in normal ovarian tissue、benign、border ovarian tumor and ovarian carcinoma Was 5%、33.3%、42.9%、67.3% respectively, and the difference was significant among the four groups(P<0.05).In ovarian carcinoma group, the positive expression of EZH2 in gradeⅠ-Ⅱ(56.7%) Was significantly lower than stageⅢ-Ⅳ(88.9%), the positive expression of EZH2 in no lymph node metastasis group (56.8%) significantly lower than lymph node metastasis (100%), and the differences were both significant (P<0.05). The expression level of EZH2 increased progressively from G1 (42.9%) and G2 (78.3%) to G3 (90.9%), and the difference was significant among the three groups(P<0.05).But no correlation was found between the expression of EZH2 and histological subtype (P>0.05).
     2.The expression of PTEN in normal ovarian tissue、benign border ovarian tumor and ovarian carcinoma Was 100%、66.7%、42.9%、38.2% respectively, and the difference was significant among the four groups(P<0.05).In ovarian carcinoma group, the positive expression of EZH2 in gradeⅠ-Ⅱ(51.4%) Was significantly lower than stageⅢ-Ⅳ(11.1%), the positive expression of EZH2 in no lymph node metastasis group (51.4%) significantly lower than lymph node metastasis (0%), and the differences were both significant (P<0.05). The expression level of EZH2 increased progressively from G1 (66.7%) and G2 (21.7%) to G3 (18.2%), and the difference was significant among the three groups(P<0.05).But no correlation was found between the expression of EZH2 and histological subtype (P>0.05).
     3. In ovarian carcinoma group, the expression of EZH2 and PTEN shows the negative correlation. (rs=-0.425, P=0.001).
     Conclusions:1.The high expression of EZH2 in ovarian cancer has positive correlation with clincal stages、histological grades and lymphaden diversion, indicating that EZH2 protein may be involved in the occurrence of ovarian cancer development, and also indicating that the protein may be associated with invasion and metastasis of ovarian cancer The detection of the protein can be estimated the prognosis of ovarian cancer.
     2.The low expression of PTEN in ovarian cancer has positive correlation with clincal stages、histological grades and lymphaden diversion,suggesting that the absence of PTEN protein may be associated with ovarian cancer occurrence and development, at the same time indicating that PTEN protein inhibits the invasion and metastasis of ovarian tumor cells。To detect the protein can understand the prognosis of ovarian cancer.
     3.EZH2 was significantly negative correlation with PTEN, suggesting that the two proteins plays an antagonistic role in the development in ovarian cancer.To detect these molecules simultan-eously, which will be more clinical value for the evaluation of mali-gnant、metastasis and prognosis of ovarian cancer.
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