title: Excision repair cross-complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin-based chemotherapy.
abstract: Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. Recent reports have suggested that ERCC1 is a predictive and prognostic marker in solid cancers treated with platinum-based chemotherapy. We performed this study to determine whether or not immunohistochemical expression of ERCC1 can predict objective tumor response and cancer-specific survival in patients with advanced urothelial carcinoma treated with cisplatin-based chemotherapy. We performed a retrospective analysis of 89 patients with advanced or recurrent urothelial cancer, who had undergone treatment at Samsung Medical Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89 patients with a known tumor response were available. ERCC1 expression was assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was positive in 49 patients (55%). The overall response rate after chemotherapy was 68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1-positive patients (p = 0.03); the difference in overall survival between patients with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not statistically significant. Other than ERCC1 expression, there was no independent prognostic factor for PFS. These results suggest a negative contribution by ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with cisplatin-based chemotherapy.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung Ha
authors.initials: KH
authors.lastname: Kim
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.forename: Hyeong Su
authors.initials: HS
authors.lastname: Kim
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Chang
authors.forename: Hyo Song
authors.initials: HS
authors.lastname: Kim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Jun
authors.forename: Jieun
authors.initials: J
authors.lastname: Uhm
authors.forename: Seong Yoon
authors.initials: SY
authors.lastname: Yi
authors.forename: Do Hyoung
authors.initials: DH
authors.lastname: Lim
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ji
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Park
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Ghee Young
authors.initials: GY
authors.lastname: Kwon
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D004720:Endonucleases / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014516:Ureteral Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin