title: Immunohistochemical molecular phenotypes of gastric cancer based on SOX2 and CDX2 predict patient outcome.
abstract: BACKGROUND
  Gastric cancer remains a serious health concern worldwide. Patients would greatly benefit from the discovery of new biomarkers that predict outcome more accurately and allow better treatment and follow-up decisions. Here, we used a retrospective, observational study to assess the expression and prognostic value of the transcription factors SOX2 and CDX2 in gastric cancer.
  
  
  METHODS
  SOX2, CDX2, MUC5AC and MUC2 expression were assessed in 201 gastric tumors by immunohistochemistry. SOX2 and CDX2 expression were crossed with clinicopathological and follow-up data to determine their impact on tumor behavior and outcome. Moreover, SOX2 locus copy number status was assessed by FISH (N = 21) and Copy Number Variation Assay (N = 62).
  
  
  RESULTS
  SOX2 was expressed in 52% of the gastric tumors and was significantly associated with male gender, T stage and N stage. Moreover, SOX2 expression predicted poorer patient survival, and the combination with CDX2 defined two molecular phenotypes, SOX2+CDX2- versus SOX2-CDX2+, that predict the worst and the best long-term patients' outcome. These profiles combined with clinicopathological parameters stratify the prognosis of patients with intestinal and expanding tumors and in those without signs of venous invasion. Finally, SOX2 locus copy number gains were found in 93% of the samples reaching the amplification threshold in 14% and significantly associating with protein expression.
  
  
  CONCLUSIONS
  We showed, for the first time, that SOX2 combined with CDX2 expression profile in gastric cancer segregate patients into different prognostic groups, complementing the clinicopathological information. We further demonstrate a molecular mechanism for SOX2 expression in a subset of gastric cancer cases.
authors.forename: Vânia
authors.initials: V
authors.lastname: Camilo
authors.forename: Rita
authors.initials: R
authors.lastname: Barros
authors.forename: Ricardo
authors.initials: R
authors.lastname: Celestino
authors.forename: Patrícia
authors.initials: P
authors.lastname: Castro
authors.forename: Joana
authors.initials: J
authors.lastname: Vieira
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: João
authors.initials: J
authors.lastname: Pinto-de-Sousa
authors.forename: Leonor
authors.initials: L
authors.lastname: David
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr, Roberto Frias s/n, 4200-465 Porto, Portugal. ralmeida@ipatimup.pt.
authors.forename: Raquel
authors.initials: R
authors.lastname: Almeida
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors