卵巢癌的二元论及其相关蛋白表达差异

Dualism of ovarian cancer and thedifference of protein expression

目的比较E-钙粘附素(E-Cadherin)、β-连环蛋白(β-catenin)、第10号染色体缺失的磷酸酶和张力蛋白同源物基因(PTEN)、磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(PKB/Akt)以及P53蛋白,在低级别浆液性癌(LGSC)、高级别浆液性癌(HGSC)、早期透明细胞癌(ECCC)与晚期透明细胞癌(ACCC)中表达的差异,探讨卵巢癌(OC)的二元论发病机制。方法收集我院2002年1月~2017年11月100例OC石蜡包埋组织,应用M.D.Anderson癌症中心的两级组织学分级系统将卵巢浆液性癌(OSC)进行分级,运用国际妇产科联盟(FIGO)分期系统将OC分期,采用免疫组织化学法检测22例LGSC、38例HGSC、20例ECCC以及20例ACCC组织中E-Cadherin、β-Catenin、PTEN、PI3K110α、p-AktSer 473以及P53蛋白表达,并结合临床病理特征进行统计分析。结果E-Cadherin、β-Catenin蛋白表达在LGSC与HGSC以及ECCC与ACCC之间比较差异均有统计学意义(P<0.05)。PTEN、PI3K110α、p-AktSer 473以及P53蛋白表达在LGSC与HGSC以及ECCC与ACCC之间比较差异均有统计学意义(P<0.05)。在LGSC与ECCC中E-Cadherin、β-Catenin蛋白表达均呈负相关(P<0.05),在HGSC中PTEN与PI3Kp110α、p-AktSer473以及P53蛋白表达均呈负相关(P<0.05),在ECCC中PTEN与PI3Kp110α以及p-AktSer473蛋白表达均呈负相关(P<0.05)。发病年龄≤50与>50、G1~2与G3以及Ⅰ~Ⅱ与Ⅲ~Ⅳ期在LGSC与HGSC以及ECCC与ACCC之间比较差异均有统计学意义(P<0.05)。结论E-Cadherin蛋白表达的缺失和β-Catenin蛋白的过度激活共同参与LGSC以及ECCC的发生、发展,而PTEN蛋白表达的缺失,PI3K110α以及p-AktSer 473蛋白的过度激活共同参与HGSC及ECCC的发生、发展,P53蛋白的过度激活参与HGSC及ACCC的发生、发展,这为探讨OC的二元论发病机制、临床诊治以及预后判断提供了依据。

Objective To compare the expression of E-Cadherin,β-Catenin,PTEN,PI3K110α,p-AktSer 473 and P53 proteins in low grade serous carcinoma(LGSC),high grade serous carcinoma(HGSC),early clear cell carcinoma(ECCC)and advanced clear cell carcinoma(ACCC),explore the dualistic mechanism of ovarian cancer(OC)and provide the basis for diagnosis and treatment of prognosis.Methods The ovarian serous carcinoma(OSC)was graded using a two-level histological grade system at M.D.Anderson cancer center.The OC stage was staged using the international union of obstetrics and gynecology(FIGO)staging system.The expression of E-Cadherin,β-Catenin,PTEN,PI3K110α,p-AktSer473 and P53 protein in 22 LGSC,38 HGSC,20 ECCC,and 20 ACCC tissues was examined by immunohistochemical method and statistically analyzed in combination with clinicopathological features.Results The expression of E-Cadherin,β-Catenin protein was statistically significant between LGSC and HGSC between ECCC and ACCC(P<0.05).The expression of PTEN,PI3K110α,p-AktSer 473 and P53 protein was statistically significant between LGSC and HGSC between ECCC and ACCC(Pp<0.05).In LGSC,the expression of E-Cadherin andβ-Catenin protein was negatively correlated(P<0.05).In HGSC,PTEN was negatively correlated with the expression of PI3K110α,p-AktSer 473 and P53 protein(P<0.05),and in ECCC,PTEN was negatively correlated with the expression of PI3K110α,p-AktSer 473(P<0.05).The difference between LGSC and HGSC between ECCC and ACCC between age≤50 and>50 was statistically significant(P<0.05).The difference between LGSC and HGSC between ECCC and ACCC between G1~2 and G3 was statistically significant(P<0.05).The difference between clinical stageⅠ-ⅡandⅢ-Ⅳwas statistically significant between LGSC and HGSC between ECCC and ACCC(P<0.05).Conclusion The deletion of E-Cadherin protein expression and the excessive activation ofβ-Catenin protein may be involved in the occurrence and development of LGSC and ECCC.The deletion of PTEN protein expression and the excessive activation of PI3K110α,and p-AktSer 473 protein may participate in the occurrence and development of HGSC and ECCC.The excessive activation of p53 protein is involved in the development of HGSC and ACCC,which provides a basis for exploring the dualistic pathogenesis,clinical diagnosis and treatment of OC.