多药耐药相关蛋白、谷胱甘肽-S-转移酶π、拓扑异构酶Ⅱα及环氧合酶-2在卵巢癌组织中的表达及其与卵巢癌患者耐药和预后的关系

目的 探讨多药耐药相关蛋白（MRP）、谷胱甘肽-S-转移酶π（GST-π）、DNA拓扑异构酶Ⅱα（TopoⅡα）及环氧合酶-2（COX-2）在卵巢癌组织中的表达情况,及其与耐药及预后的关系。方法选择北京协和医院2000至2004年间收治的上皮性卵巢癌患者60例,肿瘤细胞减灭术后经铂类和紫杉醇一线化疗6-9个疗程,随诊资料完整。其中浆乳癌35例,黏液性囊腺癌2例,透明细胞癌11例,移行细胞癌4例,子宫内膜样癌8例,患者平均年龄51．2岁。采用免疫组化法检测卵巢癌标本中MRP、GST-π、TopoⅡα及COX-2的表达情况,并分析其表达与卵巢癌患者耐药和预后的关系。结果MRP,GST-π,Topoπ和COX-2在卵巢癌标本中的阳性表达率分别为26．7％、93．3％、61．7％和78．3％。透明细胞癌组织中MRP的阳性表达率显著高于非透明细胞癌（54．5％V820．4％,P〈0．05）;Ⅲ-Ⅳ期组织中Topoπ的阳性率显著低于Ⅰ～Ⅱ期（56．6％V878．6％,P〈0．05）。将MRP阳性、GST-π强阳性、TopoⅡα阴性和COX-2强阳性表达作为4个与复发、耐药及预后不良有关的危险因素。复发组具有≥2个危险因素者显著多于未复发组（81．6％V854．5％,P〈0．05）。化疗耐药组中具有≥2个危险因素者显著多于化疗敏感组（100％V855．6％,P〈0．01）。具有≥2个危险因素者和危险因素不足2个者的3年生存率分别为69．9％和91．7％（P〉0．05）。结论MRP、GST-π、TopoⅡα及COX-2在卵巢癌组织中呈中等到高等程度的表达。具有MRP阳性、GST-π强阳性、TopoⅡα阴性和COX-2强阳性中的2个以上危险因素可作为预测卵巢癌患者复发和耐药的重要指标。

The expression of MRP, GST-pi, Topo IIalpha and COX-2 in epithelial ovarian cancer and its relationship to drug resistance and prognosis

OBJECTIVE: To study the expression of MRP, GST-pi, Topo IIalpha and COX-2 in epithelial ovarian cancer (EOC) and its relationship to drug resistance and prognosis. METHODS: Immunohistochemical method was used to study the expression of MRP, GST-pi, Topo IIalpha and COX-2 in 60 cases of epithelial ovarian cancer who were treated in PUMC Hospital from 2000 to 2004. The mean age of all patients was 51.2 years old. The histological types were 35 cases of serous adenocarcinoma, 2 cases of mucinous adenocarcinoma, 11 cases of clear cell carcinoma, 4 cases of transitional cell carcinoma and 8 cases of endometrioid carcinoma. Statistical analysis was done to determine its relationships to drug resistance and prognosis. RESULTS: The positive expression rate of MRP, GST-pi, Topo IIalpha and COX-2 in EOC was 26.7%, 93.3%, 61.7% and 78.3% respectively. The positive expression rate of MRP was significantly higher in clear cell carcinoma than that in non-clear cell carcinoma (54.5% vs 20.4%, P < 0.05); The expression of Topo IIalpha in advanced stage of EOC was significantly lower than that in early stage cases (56.6% vs 78.6%, P < 0.05). Positive expression of MRP, negative expression of Topo IIalpha, strong positive expression of GST-pi and COX-2 were seen as four risk factors for recurrence, drug-resistance and poor prognosis. More cases of recurrent group and drug-resistant group had 2 or more risk factors. The three-year survival rate of patients with 2 or more risk factors and patients with less than 2 risk factor are 69.9% and 91.7% respectively (P > 0.05). CONCLUSIONS: There are moderate or high expression of MRP, GST-pi, Topo IIalpha and COX-2 in epithelial ovarian cancer. Having 2 or more risk factors may be seen as a vital indicator to predict drug-resistance and recurrence in patients of epithelial ovarian cancer.