Yakirevich Evgeny, Sabo Edmond, Naroditsky Inna, Sova Yanina, Lavie Ofer, Resnick Murray B
Department of Pathology, Carmel Medical Center and Rappaport Faculty of Medicine, Technion University, Haifa, Israel.
Gynecol Oncol. 2006 Jan;100(1):152-9. doi: 10.1016/j.ygyno.2005.08.050. Epub 2005 Sep 29.
Multidrug resistance (MDR) to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian carcinoma patients. The MDR-related phenotype is associated with over-expression of certain drug transporters, such as P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and lung resistance protein (LRP). The aim of this study was to evaluate the extent and prognostic significance of MDR-related protein expression in ovarian serous carcinomas. In addition, we correlated expression of these proteins with the apoptosis-related proteins p53, bcl-2, and bax.
Consecutive sections from 60 cases of ovarian serous carcinoma were assessed immunohistochemically for expression of P-gp, MRP1, LRP, p53, bcl-2, and bax. The level of protein expression was scored based on staining intensity and extent.
Strong P-gp expression was observed in 12 (20%), MRP1 in 39 (65%), LRP in 27 (45%), p53 in 45 (75%), bcl-2 in 25 (41.7%), and bax in 30 (50%) of the 60 tumors. MRP1 expression was associated with both p53 and bcl-2 expressions (P = 0.01 and P = 0.03, respectively). Univariate analysis of survival revealed a significant inverse correlation between P-gp expression and patient survival (P = 0.015). Moreover, P-gp expression was significantly increased in tumors of patients unresponsive to chemotherapy (P = 0.009). Multivariate analysis revealed that only FIGO stage and P-gp expression were useful negative independent predictors of survival (P = 0.035 and P = 0.045, respectively).
Our pilot study demonstrates that P-gp expression may be a reliable independent prognostic factor of survival in patients with ovarian serous carcinoma. Moreover, P-gp immunostaining may be useful for dividing ovarian carcinoma patients into chemoresponsive and chemoresistant groups.
化疗多药耐药（MDR）是改善卵巢癌患者临床结局的主要障碍。MDR相关表型与某些药物转运蛋白的过度表达有关，如P-糖蛋白（P-gp）、多药耐药蛋白1（MRP1）和肺耐药蛋白（LRP）。本研究的目的是评估MDR相关蛋白在卵巢浆液性癌中的表达程度及其预后意义。此外，我们还将这些蛋白的表达与凋亡相关蛋白p53、bcl-2和bax进行了相关性分析。
对60例卵巢浆液性癌的连续切片进行免疫组织化学评估，以检测P-gp、MRP1、LRP、p53、bcl-2和bax的表达。根据染色强度和范围对蛋白表达水平进行评分。
在60例肿瘤中，12例（20%）观察到强P-gp表达，39例（65%）观察到MRP1表达，27例（45%）观察到LRP表达，45例（75%）观察到p53表达，25例（41.7%）观察到bcl-2表达，30例（50%）观察到bax表达。MRP1表达与p53和bcl-2表达均相关（分别为P = 0.01和P = 0.03）。生存单因素分析显示P-gp表达与患者生存呈显著负相关（P = 0.015）。此外，对化疗无反应患者的肿瘤中P-gp表达显著增加（P = 0.009）。多因素分析显示，只有国际妇产科联盟（FIGO）分期和P-gp表达是生存的有用负性独立预测因素（分别为P = 0.035和P = 0.045）。
我们的初步研究表明，P-gp表达可能是卵巢浆液性癌患者生存的可靠独立预后因素。此外，P-gp免疫染色可能有助于将卵巢癌患者分为化疗反应组和化疗耐药组。
