磷酸化AKT、NF-κBp65在上皮性卵巢癌中的表达及其意义

Expression of phosphorylated AKT and nuclear factor-kappa Bp65 in epithelial ovarian tumors and possible implications

目的:检测磷酸化AKT(P-AKT)和核转录因子(NF-κBp65)在上皮性卵巢癌中的表达并探讨它们与临床病理参数及与预后的关系。方法:用免疫组化SP法检测115例卵巢标本包括68例卵巢癌、12例卵巢交界性肿瘤、24例卵巢良性肿瘤、11例正常卵巢组织中P-AKT、NF-κBp65蛋白的表达,随访卵巢癌患者的时间为7～60个月。结果: P-AKT蛋白在卵巢癌、卵巢交界性肿瘤、卵巢良性肿瘤、正常卵巢组织(对照组)中阳性表达率分别为52．9%(36/68)、16．7%(2/12)、12．5%(3/24)、9．1%(1/11),卵巢癌P-AKT蛋白阳性表达率显著高于卵巢正常组织(X^2=7．312,P＜0．01),卵巢良性肿瘤及卵巢交界性肿瘤与正常组织间差异无统计学意义。NF-κBp65在4组中的阳性表达率依次为75%(51/68)、41．7%(5/12)、20．8%(5/24),27．2%(3/11),卵巢癌中NF-κBp65蛋白阳性表达率显著高于卵巢正常组织,差异有统计学意义(X^2=7．886,P＜0．01),卵巢良性肿瘤及卵巢交界性肿瘤与正常组织间差异无统计学意义。P-AKT、NF-κBp65蛋白在组织分化较差(X^2=6．136,P＜0．05;X^2=7．936,P＜0．01)和FIGO分期较晚(X^2=8．500,P＜0．01;X^2=9．490,P＜0．01)的卵巢癌中均有较高表达,淋巴结转移阳性的卵巢癌中P- AKT表达水平高于无淋巴结转移者(X^2=6．061,P＜0．05)。卵巢癌组织中P-AKT与NF-κBp65表达呈正相关(phi系数=0．272,P＜0．05)。P-AKT、NF-κBp65蛋白表达与卵巢癌患者生存率呈负相关,多因素Cox回归分析显示,P-AKT、NF-κBp65蛋白不是影响卵巢癌预后的独立危险因素。结论:P-AKT、NF-κBp65蛋白在卵巢癌组织中过表达,与卵巢癌的发生发展有关。P-AKT可能通过作用于其下游分子NF-κBp65促进卵巢癌细胞的恶性转化。P-AKT、NF-κB蛋白可作为判断卵巢癌预后的参考指标。

Objective：To determine the expression of P-AKT and NF-KBp65 in epithelial ovarian tumors and explore their correlation with clinicopathologic parameters and prognosis. Method：Immunohistochemical assay was used to detect the expression of P-AKT and NF- KBp65 in 115 cases of ovarian tissue, including 68 cases of ovarian cancer, 12 cases of borderline epithelial tumor,24 cases of benign epithelial tumor and 11 cases of normal ovarian tissue. All patients were followed-up in 7 - 60 months. Result：The positive rates of P-AKT expression in ovarian cancer, borderline epithelial tumors, benign epithelial tumors and normal ovarian tissues,were 52.9%, 16.7%, 12. 5% and 9.1% respectively. The positive rates of NF-KBp65 expression of those were 75.0 % ,41.7% ,20.8% and 27.2%. The positive rates of P-AKT and NF-KBp65 expression in ovarian tumors were higher than those in normal tissues. There was a close relationship between the positive rate of P-AKT and NF-KBp65 with clinical stages（ X^2= 6. 136, P 〈 0.05 ; X^2 = 7. 936, P 〈 0.01 ） and histological differentiation （ X^2 = 8. 500, P 〈 0. 01 ; X^2 = 9. 490, P 〈 0.01 ）. The positive expression of P-AKT was higher in ovarian cancer with lymph node metastasis than those without （P 〈 0.05 ）. In addition, the expression of P- AKT was significantly correlated with NF-KBp65 expression （ phi = 0. 272, P 〈 0. 05 ）. The overexpression of P-AKT and NF-kBp65 was negatively related with the survival rate of ovarian cancer patients. Neither P-AKT nor NF-kBp65 was an independent adverse prognostic factor. Conclusion：The overexpression of P-AKT and NF-kBp65 in ovarian cancer correlates with carcinogenesis and metastasis of ovarian cancer. P-AKT may contribute to malignant transformation of ovarian cancer through up-regulation of NF-kBp65 .