title: Cell cycle regulators, APC/beta-catenin, NF-kappaB and Epstein-Barr virus in gastric carcinomas.
abstract: OBJECTIVE
  To evaluate the clinicopathological value of cell cycle regulators, the Wnt pathway, the NF-betaB pathway and Epstein-Barr virus (EBV) and to assess their relationships in gastric carcinoma.
  
  
  METHODS
  We investigated cell cycle regulators (p53, p21, Rb), APC, beta-catenin and NF-kappaB using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma.
  
  
  RESULTS
  p53 overexpression was more frequently observed in advanced gastric carcinoma and lymph node metastasis than in early carcinoma or in the absence of metastasis (p < 0.05). p21 loss was positively correlated with APC loss, but inversely correlated with beta-catenin nuclear accumulation and NF-kappaB positivity (p < 0.05). EBV positive gastric carcinomas were located in the upper third of the stomach, and more were of the diffuse or mixed types than the EBV negative group (p < 0.05). EBV infection was positively correlated with p21 loss and APC loss and inversely correlated with beta-catenin alteration (p < 0.05). In multivariate analysis, patient age, TNM stage and p53 were independent prognostic factors for gastric carcinoma.
  
  
  CONCLUSIONS
  p53 status is a prognostic marker for gastric carcinoma. p21, APC, beta-catenin and NF-kappaB may be functionally interrelated in gastric carcinogenesis. Loss of p21 and APC may be involved in the carcinogenesis of EBV positive gastric carcinomas.
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Kim
authors.forename: Sun-Ju
authors.initials: SJ
authors.lastname: Byun
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000821:virology; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D015897:Comorbidity; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015996:Survival Rate; D051176:beta Catenin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D016328:NF-kappa B; D051176:beta Catenin