卵巢恶性肿瘤中GST-π表达与肿瘤内在性耐药及患者预后关系的研究

Study on the determination of glutathione Stransferase π class expression in ovarian malignant tumors and its relationship with intrinsic drug resistance and patient's prognosis

目的：探讨谷胱甘肽Ｓ－转移酶π型（ＧＳＴ－π）在卵巢恶性肿瘤组织中的表达及其与肿瘤内在性耐药和患者预后的关系。方法：应用免疫组化ＳＰ法检测４５份卵巢恶性肿瘤组织和１０份正常卵巢组织中ＧＳＴ－π的表达，结合肿瘤细胞体外药物敏感试验结果和患者２ａ随访结果。结果：１．４５份卵巢恶性肿瘤组织ＧＳＴ－π阳性表达率为１００％，１０份正常卵巢组织仅２份呈弱阳性。２．１８份卵巢恶性肿瘤组织ＧＳＴ－π染色程度（＋）、（）、（）三组之间阿霉素对肿瘤细胞的抑制率有统计学差异（Ｐ＜０．０５），其中（）组抑制率明显低于（＋）组（Ｐ＜０．０５）。其余５种药物对肿瘤细胞抑制率差异无显著性（均Ｐ＞０．０５）。３．２８例Ⅲ期卵巢上皮性癌患者２ａ存活率为３９．３％，存活时间≥２ａ和＜２ａ两组ＧＳＴ－π表达差异有显著性（Ｐ＜０．０１），前者染色程度明显弱于后者。结论：ＧＳＴ－π表达在卵巢恶性肿瘤对阿霉素内在性耐药中起重要作用，而与顺铂、卡铂、５－ＦＵ、更生霉素、长春新碱内在性耐药无关。ＧＳＴ－π表达高提示卵巢癌患者预后差，可供临床评价患者预后时参考。

Objective:To study the immunohistochemical expression of glutathione Stransferase pi class(GSTπ)in ovarian malignant tumors,and its relationship with intrinsic drug resistance and patient's prognosis.Methods:45 specimens of previously untreated patients with ovarian malignant tumors were collected to determine the expression of GSTπ by using immunohistochemical method,in which 18 specimens had been screened in vitro with chemosensitivity assay to 6 single chemotherapeutical drugs.28 cases with advanced stages were followed up for at least two years after operation.10 specimens of normal ovarian tissues served as controls.Results:1.All of 45 specimens of ovarian malignant tumors showed positive staining for GSTπ,and the staining was diffusely in the cytoplasm.No positive staining was found in the control except 2 specimens with weak staining.2.According to GSTπ staining intensity,18 specimens of ovarian malignant tumors were classified into three groups:(+),(),and ().There was significant difference of the inhibitory rate of adriamycin to tumor cells among three groups(P<0.05),in which the drug inhibitory rate in Group()was much lower than that in Group(+)(P<0.05).No significant difference of the other five drug inhibitory rates was found among the three groups.3.The patient's 2year survival rate of 28 cases with advanced ovarian cancer was 39.3%(11/28).With respect to staining intensity for GSTπ,the patient's survival rates in groups of weak,moderate,and strong staining were 80%(4/5),54.5%(6/11),and 8.3%(1/12)respectively.The staining intensity in group of survival period≥2 years was lower than that in group of survival period <2 years(P<0.01).Conclusions:1.The role of GSTπ is important in intrinsic drug resistance to adriamycin in ovarian malignant tumors,but not to cisplatin,carboplatin,5fluorouracil,kengshenmycin,and vincristine.2.GSTπ overexpression is a useful marker of a poor prognosis for patients with ovarian cancer.