Cell cycle regulators, APC/beta-catenin, NF-kappaB and Epstein-Barr virus in gastric carcinomas.
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.
Kim
Bomi
B
Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea.
Byun
Sun-Ju
SJ
Kim
Young A
YA
Kim
Ji Eun
JE
Lee
Byung Lan
BL
Kim
Woo Ho
WH
Chang
Mee Soo
MS
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
D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D016328:NF-kappa B; D051176:beta Catenin