ERCC1and BRCA1Expressions In The Tissues Of Urothelial Tumors And Its Relationship With Clinical Significance Of Platinum-based Phemotherapy

Objective:To explore the expressions of excision repair cross-complementing gene1(ERCC1)and breast cancer susceptibility gene1(BRCA1)in the tissues of urothelial cancer and its clinical significance; To evaluate the therapeutic effect and prognosis of Gemcitabine combined with Oxaliplatin on advanced or metastatic uroedthelial carcinoma.Methods:A total of42patients pathologically confirmed with advanced or metastatic urothelial carcinoma (23cases of bladder cancer,11cases of renal pelvic carcinoma, and8cases of ureteral carcinoma) were reviewed. Karnofsky score for each patient before therapy was=60. Combined treatment with Gemcitabine and Oxaliplatin regimen was as follows:Gemcitabine700mg/m2, iv infusion at day1,8and day15; Oxaliplatin100mg/m2, iv infusion at day2. The regimen was administered for more than2cycles (every4weeks) and the response rate was evaluated. ERCC1and BRCA1expressions in the tissues of urothelial cancer were measured by immunohistochemistry.Results:According to WHO evaluation criteria on therapeutic effectiveness,? patients (16.67%) had complete response,13patients (30.95%) had partial response,14cases (33.33%) remained stable status,and8cases (19.05%) had progression. The overall response rate was47.62%.The positive rate of ERCC1expression was47.6%,and was not significantly correlated with age、sex、somking、TNM and histologic grade. Compared with ERCC1positive patients, ERCC1negative patients had longer median survival time(MST)with statistical difference(P<0.05). The positive rate of BRCA1expression was64.3%and was not significantly correlated with age、sex、 somking、TNM and histologic grade. Compared with BRCA1positive patients, BRCA1negative patients had longer MST, but the difference was not significant(P>0.05). Compared with ERCC1positive plus BRCA1positive patients,ERCC1negative plus BRCA1negative patients had significantly longer MST(P<0.05). The positive expression of ERCC1and BRCA1had a significant positive correlation with urothelial cancer(r=0.313, P=0.044).Conclusions:Combined treatment with Gemcitabine and Oxaliplatin is effective for advanced or metastaticurothelial carcinoma, with mild and tolerable toxicities.ERCC1negative patients with oxaliplatin-based chemotherapy may obtain survival benefit, but the survival benefit in BRCAl negative patients was not obvious. Expression levels of ERCC1and BRCA1might be useful in the choice of chemotherapy regimes and evaluation of prognosis for patients with urothelial cancer.