title: Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy.
abstract: OBJECTIVE
  Neoadjuvant chemotherapy followed by surgery is the standard of care for patients with gastro-oesophageal adenocarcinoma. Previously, we validated the utility of the tumour regression grade (TRG) as a histopathological marker of tumour downstaging in patients receiving platinum-based neoadjuvant chemotherapy. In this study we profiled key DNA repair and damage signalling factors and correlated them with clinicopathological outcomes, including TRG response.
  
  
  RESULTS
  Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays (TMAs). The first set consisted of 142 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 103 gastric/gastro-oesophageal cancer cases exposed to preoperative platinum-based chemotherapy. Expressions of ERCC1, XPF, FANCD2, APE1 and p53 were investigated using immunohistochemistry. In patients who received neoadjuvant chemotherapy, favourable TRG response (TRG 1, 2 or 3) was associated with improvement in disease-specific survival (P=0.038). ERCC1 nuclear expression correlated with lack of histopathological response (TRG 4 or 5) to neoadjuvant chemotherapy (P=0.006) and was associated with poor disease-specific (P=0.020) and overall survival (P=0.040).
  
  
  CONCLUSIONS
  We provide evidence that tumour regression and ERCC1 nuclear protein expression evaluated by immunohistochemistry are promising predictive markers in gastro-oesophageal cancer patients receiving neoadjuvant platinum-based chemotherapy.
authors.affiliation: Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK.
authors.forename: K R
authors.initials: KR
authors.lastname: Fareed
authors.forename: A
authors.initials: A
authors.lastname: Al-Attar
authors.forename: I N
authors.initials: IN
authors.lastname: Soomro
authors.forename: P V
authors.initials: PV
authors.lastname: Kaye
authors.forename: J
authors.initials: J
authors.lastname: Patel
authors.forename: D N
authors.initials: DN
authors.lastname: Lobo
authors.forename: S L
authors.initials: SL
authors.lastname: Parsons
authors.forename: S
authors.initials: S
authors.lastname: Madhusudan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017671:Platinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D047368:Tumor Burden / Q000502:physiology*
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases
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