title: ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy.
abstract: BACKGROUND
  Adjuvant chemotherapy is gaining an increasing role in resectable gastric cancer. Customizing chemotherapy on the basis of chemosensitivity may improve outcome, and putative predictive molecular markers have been mostly evaluated in Asian patients. We profiled key DNA and damage signaling factors and correlated them with outcome, in a European cohort.
  
  
  METHODS
  Formalin-fixed tumor samples obtained from surgical specimens of patients treated with adjuvant cisplatin-based chemotherapy for gastric cancer were analyzed. Immunohistochemistry (IHC) was performed to analyze excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TS) expression, and p53 mutations were detected with direct sequencing.
  
  
  RESULTS
  Among the 68 patient recruited, the median age was 69 (range 30-74), and UICC stage was III in 44 patients (65 %). With a median follow-up of 40.5 months, disease-free and overall survival were 18.0 (95 % CI 13.4-22.76) and 56 months (95 % CI 44.87-67.13), respectively. ERCC1 score was 0 in 14 out 67 (21 %) cases, 1 in 19 (28 %), 2 in 20 (30 %) and 3 in 14 cases (21 %). Longer overall survival (p = 0.04) was found in patients categorized as ERCC1 negative by IHC according to median score. TS score was 0 in 16 out 67 (24 %) cases, 1 in 27 (40 %), 2 in 16 (24 %) and 3 in 8 cases (12 %). Mutations of p53 were found in 21 out 66 (32 %) cases. Neither TS nor p53 were found to correlate with outcome.
  
  
  CONCLUSIONS
  Excision repair cross-complementing gene 1 by IHC might predict patients more likely to benefit from adjuvant cisplatin-based chemotherapy in curatively resected gastric cancer. In patients exhibiting ERCC1 positive tumors, alternative regimens should be evaluated.
authors: Oncology Institute of Southern Switzerland, 6500, Bellinzona, Switzerland. Sara.Dedosso@eoc.ch
authors: Sara
authors: S
authors: De Dosso
authors: Elena
authors: E
authors: Zanellato
authors: Martina
authors: M
authors: Nucifora
authors: Renzo
authors: R
authors: Boldorini
authors: Angelica
authors: A
authors: Sonzogni
authors: Roberto
authors: R
authors: Biffi
authors: Nicola
authors: N
authors: Fazio
authors: Eraldo
authors: E
authors: Bucci
authors: Ottavio
authors: O
authors: Beretta
authors: Stefano
authors: S
authors: Crippa
authors: Piercarlo
authors: P
authors: Saletti
authors: Milo
authors: M
authors: Frattini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D012189:Retrospective Studies; D013270:Stomach / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin