title: Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy.
abstract: OBJECTIVE
  Excision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.
  
  
  METHODS
  Thirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.
  
  
  RESULTS
  Pathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012-0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2-11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤ 60 years) (HR 3.4, 95% CI 1.2-9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014-0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9-19.9, P = 0.002) were significantly associated with OS.
  
  
  CONCLUSIONS
  Our results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.
authors.affiliation: Department of Urology, Ankara Ataturk Education and Research Hospital, Ankara, Turkey. Electronic address: mfuatozcan@hotmail.com.
authors.forename: Muhammet Fuat
authors.initials: MF
authors.lastname: Ozcan
authors.forename: Omer
authors.initials: O
authors.lastname: Dizdar
authors.forename: Nazmiye
authors.initials: N
authors.lastname: Dincer
authors.forename: Serdar
authors.initials: S
authors.lastname: Balcı
authors.forename: Gulnur
authors.initials: G
authors.lastname: Guler
authors.forename: Bahri
authors.initials: B
authors.lastname: Gok
authors.forename: Gokhan
authors.initials: G
authors.lastname: Pektas
authors.forename: Mehmet Metin
authors.initials: MM
authors.lastname: Seker
authors.forename: Sercan
authors.initials: S
authors.lastname: Aksoy
authors.forename: Cagatay
authors.initials: C
authors.lastname: Arslan
authors.forename: Suayib
authors.initials: S
authors.lastname: Yalcin
authors.forename: Mevlana Derya
authors.initials: MD
authors.lastname: Balbay
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004720:Endonucleases / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin