title: Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer.
abstract: BACKGROUND
  The invasive tumour front may provide prognostic information. We examined the relationship between the presence of cancer stem cells (CSCs) at the invasive tumour front and prognosis in gastric cancer (GC).
  
  
  METHODS
  CD44 is a CSC marker; accordingly, CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression were examined in 123 resected primary GCs and the clinical significance of CSCs at the invasive tumour front was analysed.
  
  
  RESULTS
  Thirteen (10.6%), 79 (64.2%), and 47 (38.2%) GCs were CD44s-, CD44v6-, and CD44v9-positive, respectively. Patients with CD44-positive expression at the invasive tumour front had significantly poorer disease-specific survival than those with negative expression (CD44s: P<0.00001, CD44v6: P=0.013, CD44v9: P=0.0002). CD44s expression at the invasive tumour front was an independent prognostic factor in resectable GC patients (hazard ratio=3.13; 95% confidence interval, 1.09-9.01; P=0.035) and was significantly associated with peritoneal (P<0.001), lymphatic (P<0.001), and haematogenous recurrences (P=0.008). In addition, the number of CD44 isoforms expressed in cancer cells at the invasive tumour front was associated with patient prognosis. No conventional clinicopathological factors were independently associated with CD44 expression at the invasive tumour front.
  
  
  CONCLUSIONS
  CD44-positive cancer stem-like cells at the invasive tumour front indicate poor survival and can be a unique biological prognostic factor for GC.
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kodama
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murata
authors.affiliation: Division of Diagnostic Pathology, Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Japan.|Division of Diagnostic Pathology, Kansai Medical University, Osaka, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kaida
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Takebayashi
authors.affiliation: Division of Diagnostic Pathology, Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.affiliation: Department of Surgery, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Masaji
authors.initials: M
authors.lastname: Tani
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012008:Recurrence; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors