title: Sequential expression of putative stem cell markers in gastric carcinogenesis.
abstract: BACKGROUND
  Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers.
  
  
  METHODS
  We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression.
  
  
  RESULTS
  We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy.
  
  
  CONCLUSIONS
  CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.
authors.affiliation: Cancer Science Institute, National University Health System and Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: C W
authors.initials: CW
authors.lastname: Ong
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: S
authors.initials: S
authors.lastname: Srivastava
authors.forename: B
authors.initials: B
authors.lastname: Yan
authors.forename: C L
authors.initials: CL
authors.lastname: Cheng
authors.forename: W P
authors.initials: WP
authors.lastname: Yong
authors.forename: S L
authors.initials: SL
authors.lastname: Chan
authors.forename: K G
authors.initials: KG
authors.lastname: Yeoh
authors.forename: B
authors.initials: B
authors.lastname: Iacopetta
authors.forename: M
authors.initials: M
authors.lastname: Salto-Tellez
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D010455:Peptides / Q000032:analysis / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D011237:Predictive Value of Tests; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C491297:MSI1 protein, human; D009419:Nerve Tissue Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D016601:RNA-Binding Proteins