title: Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy.
abstract: OBJECTIVE
  To examine cytokeratin-18 (CK-18) and caspase-cleaved CK-18 expression in tumours and correlate with clinicopathological outcomes including tumour regression grade (TRG) response.
  
  
  METHODS
  Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays. The first set consisted of 122 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 97 gastric/gastro-oesophageal cancer cases exposed to pre-operative platinum-based chemotherapy. Expression of CK-18 and caspase-cleaved CK-18 was investigated using immunohistochemistry.
  
  
  RESULTS
  CK18 was commonly expressed in gastro-oesophageal tumours (92.6%). Fifty-six point seven percent of tumours previously exposed to neoadjuvant chemotherapy were positive for caspase-cleaved CK-18 expression compared to only 24.6% of tumours not previously exposed to neoadjuvant chemotherapy (P = 0.009). In patients who received neoadjuvant chemotherapy, caspase-cleaved cytokeratin-18 expression correlated with favourable TRG response (TRG 1, 2 or 3, P = 0.043).
  
  
  CONCLUSIONS
  This is the largest study to date of CK-18 and caspase-cleaved CK-18 expression in gastro-oesophageal tumours. We provide the first evidence that caspase-cleaved CK-18 predicts tumour regression with neoadjuvant 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 University Hospitals, Nottingham NG5 1PB, United Kingdom.
authors.forename: Khaleel R
authors.initials: KR
authors.lastname: Fareed
authors.forename: Irshad N
authors.initials: IN
authors.lastname: Soomro
authors.forename: Khalid
authors.initials: K
authors.lastname: Hameed
authors.forename: Arvind
authors.initials: A
authors.lastname: Arora
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
authors.forename: Simon L
authors.initials: SL
authors.lastname: Parsons
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Madhusudan
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D020169:Caspases / Q000502:physiology*; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000032:analysis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology
chemical_list: D053538:Keratin-18; D020169:Caspases