Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma

World J Gastroenterol. 2004 Jul 1;10(13):1862-6. doi: 10.3748/wjg.v10.i13.1862.


Aim: To assess the expression of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), p53 and Ki-67 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and clarify the relationship between COX-2 expression and iNOS or p53 expression in these patients.

Methods: The expressions of COX-2, iNOS, p53 and Ki-67 were detected in 32 gastric MALT lymphoma specimens and 10 adjacent mucosal specimens by immunohistochemical Envision method.

Results: COX-2 and iNOS expressions were significantly higher in gastric MALT lymphoma tissues than those in adjacent normal tissues. The expression of COX-2 was observed in 22 of 32 cases of MALT lymphoma tissues (68.8%). A positive cytoplasmic immunoreactivity for iNOS was detected in 17 of 31 cases (53.1%). COX-2 expression in gastric MALT lymphoma tissues was positively correlated with iNOS expression (r=0.448, P=0.010) and cell proliferative activity analyzed by Ki-67 labeling index (r=0.410, P=0.020). The expression of COX-2 protein did not correlate with age, sex, stage of disease, lymph node metastasis or differentiation. The accumulation of p53 nuclear phosphoprotein was detected in 19(59.4%) of tumors. p53 protein was expressed in 11 of 23 assessed LG tumors and in 8 of 9 assessed HG tumors. The difference of p53 positivity was found statistically significant between LG and HG cases (P=0.0302). The p53 accumulation correlated with advanced clinical stage (stage III+IV vs stage I+II, P=0.017). There was a significant positive correlation between COX-2 expression and p53 accumulation status (r=0.403, P=0.022). The mean PI of Ki-67 in each grade group were 36.0+/-7.73% in HG and 27.4+/-9.21% in LG. High-proliferation rate correlated with HG tumors (r=0.419, P=0.017). The correlation coefficient showed a significant positive correlation between PI and COX-2 expression in MALT lymphoma patients (r=0.410, P=0.020).

Conclusion: COX-2 expresses in the majority of gastric MALT lymphoma tissues and correlates with cellular proliferation and iNOS expression. COX-2 overexpression is closely associated with p53 accumulation status. iNOS and COX-2 may play a synergistic role in the pathogenesis of gastric MALT lymphoma.

MeSH terms

  • Biomarkers, Tumor
  • Cyclooxygenase 2
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Humans
  • Immunohistochemistry
  • Isoenzymes / metabolism*
  • Ki-67 Antigen / metabolism
  • Lymphoid Tissue / metabolism
  • Lymphoid Tissue / pathology
  • Lymphoma, B-Cell, Marginal Zone / metabolism*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Membrane Proteins
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Protein p53 / metabolism


  • Biomarkers, Tumor
  • Isoenzymes
  • Ki-67 Antigen
  • Membrane Proteins
  • Tumor Suppressor Protein p53
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases