title: Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus.
abstract: BACKGROUND
  Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression.
  
  
  METHODS
  We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis.
  
  
  RESULTS
  Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (P<0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P=0.020), pN number (P=0.001), and CK18 expression (P=0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P=0.045).
  
  
  CONCLUSIONS
  CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Makino
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: A
authors.initials: A
authors.lastname: Takeno
authors.forename: M
authors.initials: M
authors.lastname: Shirakawa
authors.forename: H
authors.initials: H
authors.lastname: Miyata
authors.forename: S
authors.initials: S
authors.lastname: Takiguchi
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Nishida
authors.forename: N
authors.initials: N
authors.lastname: Matsuura
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053538:Keratin-18 / Q000032:analysis*; D053533:Keratin-8 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D053538:Keratin-18; D053533:Keratin-8