Expression of nitric oxide synthase, cyclooxygenase, and p53 in different stages of human gastric cancer

The present study evaluated the significance of nitric oxide synthase (NOS) , cyclooxygenase (COX) expression and p53 status in 55 patients with gastri c adenocarcinoma and relationship of these molecular markers to tumor chara cteristics and metastatic potential, Immunohistochemical technique was used to identify the cellular location and distribution of the enzymes in the s pecific cells of gastric tumors. In gastric cancer tissue, the expression o f inducible enzymes, iNOS and COX-2, increased significantly with increasin g tumor stage (P = 0.015, P = 0.001, respectively), size (P = 0.025, P = 0. 001, respectively) and the presence of metastases (P = 0.002, P = 0.015, re spectively). The expression of constitutive enzymes, ecNOS and COX-1, follo wed the opposite pattern. COX-1 was significantly reduced in advanced gastr ic tumors (P = 0.007) and tumors larger than 5 cm (P = 0.007). Reduced expr ession of ecNOS was also observed in advanced gastric tumors; however, this did not reach statistical significance. 53% of gastric tumors showed accum ulation of p53. This was significantly higher in advanced tumors (P = 0.004 ), larger than 5 cm (P = 0.015) with metastases (P < 0.001). Gastric tumors positive for accumulation of p53 had significantly stronger expression of iNOS (P = 0.018) and COX-2 (P = 0.01) enzymes than tumors negative for this nucleophosphoprotein. We conclude, that tumor-associated nitric oxide prod uction, as well as COX-2 overexpression, may promote gastric cancer progres sion by providing a selective growth advantage to tumor cells with non-func tioning p53. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.