p-mTOR和p-4EBP1蛋白在卵巢上皮性癌组织中的表达及意义

目的 探讨卵巢上皮性癌组织中磷酸化雷帕霉素靶蛋白（p-mTOR）及磷酸化起始因子4E结合蛋白1（p-4EBP1）的表达变化及二者的相关性.方法 通过免疫组织化学染色法检测142例卵巢组织标本,包括正常卵巢组织20例、卵巢良性上皮肿瘤组织26例、卵巢交界性上皮肿瘤组织24例及卵巢上皮性癌组织72例,观察p-mTOR及p-4EBP1的表达情况变化.结果 （1）p-mTOR在正常卵巢组织、卵巢良性上皮肿瘤组织、卵巢交界性上皮肿瘤组织及卵巢上皮性癌组织中总体阳性率分别为5.0%（1/20）、11.5%（3/26）、25.0%（6/24）、48.6%（35/72）,四组间比较,差异有统计学意义（P〈0.05）.在卵巢上皮性癌中有淋巴结转移患者标本中p-mTOR阳性表达率为59.1%（26/44）,明显高于无淋巴结转移患者标本（32.1%,9/28）,差异有统计学意义（P〈0.05）.在卵巢上皮性癌临床分期中,高分期组（Ⅲ＋Ⅳ期）p-mTOR阳性表达率（55.6%,30/54）显著高于低分期组（Ⅰ＋Ⅱ期）（27.8%,5/18）,差异有统计学意义（P〈0.05）.（2）p-4EBP1在正常卵巢组织、卵巢良性上皮肿瘤组织、卵巢交界性上皮肿瘤组织及卵巢上皮性癌组织中总体阳性率分别为5.0%（1/20）、19.2%（5/26）、29.2%（7/24）、59.7%（43/72）,四组间比较,差异有统计学意义（P〈0.05）.在卵巢上皮性癌中有淋巴结转移患者标本中p-4EBP1阳性表达率为70.5%（31/44）,明显高于无淋巴结转移患者标本（42.9%,12/28）,差异有统计学意义（P〈0.05）.在卵巢上皮性癌临床分期中,高分期组（Ⅲ＋Ⅳ期）p-4EBP1阳性表达率（66.7%,36/54）显著高于低分期组（Ⅰ＋Ⅱ期）（38.9%,7/18）,差异有统计学意义（P〈0.05）.（3）p-mTOR及p-4EBP1在卵巢上皮性癌组织中表达呈正相关（r=0.402,P〈0.05）.结论 p-mTOR和p-4EBP1蛋白在卵巢上皮性癌中高表达,提示二者参与了卵巢上皮性癌的发生、发展.p-mTOR和p-4EBP1蛋白在卵巢上皮性癌组织中的表达呈正相关,提示在卵巢上皮性癌的发生、发展中二者起协同作用.

Expression and significance of p-mTOR and p-4EBP1 in epithelial ovarian cancer

Objective To investigate the expression changes of p-mTOR and p-4EBP1 in epithelial ovarian cancer, as well as the relations between the two proteins. Methods Immunohistochemical staining was adopted to detect 142 cases of ovari- an tissues including 20 normal ovarian tissues, 26 benign epithelial ovarian tumor, 24 borderline epithelial ovarian tumor and 72 epithelial ovarian cancer. The expression changes of p-mTOR and p-4EBPl in the two groups were observed. Results （ 1 ）The positive expression rate of p-mTOR in normal ovarian tissues ,benign epithelial ovarian tumor, borderline epithelial ovarian tumor and epithelial ovarian cancer were 5.0% （1/20）, 11.5% （3/26）, 25.0% （6/24）, 48.6% （35/72） respectively, the difference among the four groups were statistically significant （P〈0.05）. In the epithelial ovarian cancer, the positive expression rate of p-mTOR in patients with lymph node metastasis was 59.1% （26/44）, which was obviously higher than that in patients without lymph node metas tasis （32.1%, 9/28 ）, and the difference had statistical significance （P〈0.05）. In the clinical stages of epithelial ovarian cancer, the positive expression rate of p-roTOR was 55.6% （30/54） in high-grade group （grade III ＋ IV ）, which was obviously higher than the rate in low-grade group （group I ＋ II ） （27.8%, 5/18 ） of 27.8% （5/18 ）, and the difference had statistical significance （P〈0.05）. （2） The overall positive expression rate of p-4EBP1 in normal ovarian tissues, benign epithelial ovarian tumor, borderline epithelial ovarian tumor and epithelial ovarian cancer were 5.0% （1/20）, 19.2% （5/26）, 29.2% （7/24）, 59.7% （43/72） respectively, the expression difference among the four groups were statistically significant （P〈0.05）. In the epithelial ovarian cancer, the positive expression rate of p-4EBP1 in patients with lymph node metastasis was 70.5% （31/44） ,which was significantly higher that that in patients without lymph node metastasis （42.9%, 12/28 ）, and the difference had statistical significance （P〈0.05）. In the clinical stages of epithelial ovarian cancer, the positive rate of p-4EBP1 was 66.7% （36/54） in high-grade group （group m ＋iv ）, which was prominently higher than the rate in low-grade group （grade I ＋ II ） of 38.9% （7/18）,and the difference had statistical significance （P〈 0.05）. （3）The expression of p-mTOR and p-4EBP1 in epithelial ovarian cancer was positively correlated （r=0.402,P〈0.05）. Con- clusion The high expression of p-mTOR and p-4EBP1 in epithelial ovarian cancer suggests that p-mTOR and p-4EBP1 play a role in the growth, proliferation and metastasis of epithelial ovarian cancer; the positive correlation between p-roTOR and p-4EBP1 in tissues of epithelial ovarian cancer shows they play synergistic effect in the growth and development of epithelial ovarian cancer.