title: Increased proliferative activity caused by loss of p21(WAF1/CIP1) expression and its clinical significance in patients with early-stage gastric carcinoma.
abstract: BACKGROUND
  Recurrences of gastric carcinoma are likely to take on a variety forms, even after patients undergo curative resection for early-stage gastric carcinoma. It is important to identify the biologic markers that predict tumor progression and survival in these patients. Proliferating cell nuclear antigen (PCNA) acts as a processivity factor for DNA polymerase delta, which is involved directly in DNA synthesis, and the PCNA level is correlated with the proliferative state of cells. p21(WAF1/CIP1) interacts with PCNA to inhibit DNA synthesis and plays a central role in regulating the cell cycle. The authors investigated patients with early-stage gastric carcinoma to determine the clinical significance of proliferative activity and p21 expression.
  
  
  METHODS
  Tissue specimens from 133 Japanese patients with early-stage gastric carcinoma that invaded the submucosal layer were immunostained with a monoclonal antibody against PCNA and p21(WAF1/CIP1), and the correlations between the PCNA labeling index and p21(WAF1/CIP1) expression as well as clinicopathologic factors were investigated.
  
  
  RESULTS
  The PCNA labeling index varied from 9.9% to 81.4%, (mean, 31.2%). The incidence of p21 positive expression was 87 of 133 patients (65.4%). The patients with a high labeling index had a significantly higher rate of lymph node metastasis (P < 0.01) and loss of p21(WAF1/CIP1) expression (P < 0.05) compared with the patients with a low labeling index. The 5-year survival rate for patients in the high labeling index group (87.0%) was significantly lower compared with the 5-year survival rate for the patients in the low labeling index group (98.6%; P < 0.05).
  
  
  CONCLUSIONS
  Loss of p21(WAF1/CIP1) expression contributes to the amplification of proliferative activity in patients with early-stage gastric carcinoma. Estimation of the proliferative activity of early-stage gastric carcinoma provides information on lymph node metastasis and prognosis. Even after patients undergo curative resection, those with early-stage gastric carcinoma should be followed closely.
authors.affiliation: Department of Surgery, Saga Prefectural Hospital Koseikan, Saga, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Koji
authors.initials: K
authors.lastname: Irie
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yonemura
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugimachi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen