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Study On The Relation Between ERCC1, ATF-2 And Cisplatin Resistance In Ovarian Epithelial Carcinoma

Posted on:2007-12-18Degree:MasterType:Thesis
Country:ChinaCandidate:H Y WangFull Text:PDF
GTID:2144360182491795Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Objective:To observe the expression of ERCC1 and ATF-2 in the paraffin specimens and fresh tissues of ovarian epithelial carcinoma and to explore the relation between the expression of ERCC1, ATF-2 and cisplatin resistance in ovarian epithelial carcinoma;to assess the forecasting value of the two genes, which may provide basis for individual treatment of ovarian carcinoma patients in clinic.Methods:The study includes two parts. In the first part the expression of two proteins were examined in 56 ovarian carcinoma specimens by SP immuohistochemical method;the second part we applied the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) technique to assess the mRNA levels of two genes in ovarian cancer tissues, their correlations to chemoresistance were analyzed by SPSS 12.0 statistical program, and studied the predictive value to chemoresistance in ovarian carcinoma.Results:1. Among those 56 cases, ERCC1 and ATF-2 expression levels did not show any association with patient age, operational stage, histology type and ascitic fluid. The positive expression rates of ERCC1 and ATF-2 proteins in ovarian carcinoma specimens were respectively 58.93% and 50.00%, and the expressions in cisplatin resistant patients were higher than that of cisplatin sensitive ones, with significantly difference between the two groups (P<0.05), immunohistochemical cumulativescore in chemoresistant patients obviously higher than that of chemosensitive ones (P <0.05);There was a positive correlation between the protein expression of ERCCl and ATF-2 (r=0.607, P=0.00Q), namely, the increased expression of ATF-2 was along with ERCCl expression improved. ROC analysis was used to assess the predictive value of ERCCl and ATF-2 protein expressions, the areas below ROC curve were 0.685 and 0.727 respectively, with statistical significance (P=0.018, 0.004).2. The range of ERCCl/p-actin mRNA level in fresh tissues of untreated ovarian carcinoma was from 0.294 to 3.060, and the highest level was approximately 10.4 times than that of the lowest;the ATF-2/p-actin mRNA level range was from 0.119 to 2.276, and the highest level was 19.1 times than that of the lowest;the mean of ERCCl and ATF-2 mRNA level was 0.999 and 0.852 respectively.3. 24 ovarian carcinoma patients were divided into two groups by the integral mean of ERCCl and ATF-2 mRNA level, I.E 1.000 and 0.900, 7 in 9 patients in ERCCl high level group were resistant to chemotherapy, whereas only 3 in 15 patients in low level group were resistant. 6 in 10 patients in ATF-2 high level group were resistant to chemotherapy, 4 in 14 patients in low level group were resistant. Comparing with follow-up visit information of chemotherapy, the coincidence rates were 79.17% and 66.67%, the differences had no statistical significance (P>0.05);7 patients with ERCCl and ATF-2 mRNA level higher than their dividing levels were resistant to chemotherapy, whereas 3 in 17 patients with ERCCl and ATF-2 mRNA level lower than their dividing levels were resistant to chemotherapy. There was a significant difference (i*=0.000).4. There was a positive correlation between ERCCl/p-actin mRNA level and chemoresistance (rs=0.769, P=0.000), however there was not an evident relevance between ATF-2/f3-actin mRNA level and cisplatin resistance (rs=0.391, P=0.059);and the combination with ERCCl and ATF-2 detected simultaneously (rs=0.847, P=0.000) was stronger than that of ERCCl detected alone.5. The RT-PCR results showed up ERCCl and ATF-2 mRNA levels in 10 chemoresistant patients were 1.565±0.714 and 1.132±0.645, higher than that of chemosensitive patients (P 0.05).Conclusions:1. The expressions of ERCCl and ATF-2 in ovarian epithelial carcinoma tissues were associated with cisplatin resistance. The expressions of two genes in chemoresistant patients were higher than that of chemosentitive ones.2. There was a positive correlation between cisplatin resistance and ERCCl/p-actin mRNA level, and there was a positive correlation between ERCCl and ATF-2, the increasing expression of ATF-2 may induce the expression of ERCCl by the mechanism of molecule regulation, the combination with ERCCl and ATF-2 detected simultaneously was more exact than that of ERCCl detected alone.3. The ERCClmRNA level has a certain predictive value to cisplatin resistance in ovarian epithelial carcinoma, we can determine whether cisplatin resistance in ovarian carcinoma according to ERCCl/p-actin mRNA=1.000;in order to guide planning individual chemotherapy scheme for clinical treatment;we may substitute immunohistochemical technique to predict cisplatin resistance for the gene examination (RT-PCR), patients may be originally resistant to chemoresistance if the expression of ERCCl protein was positive in their cancer tissues.
Keywords/Search Tags:ovarian carcinoma, cisplatin, ERCC1, ATF-2, drug resistance
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