Expression of COX-2 in stomach carcinogenesis.
BACKGROUND
Gastric cancer is a frequent cause of cancer in Brazil. The understanding of gastric carcinogenesis is not completely known but the progress of the molecular biology has provided that the initiation and progression of gastric cancer process is a consequence of a cumulative series of multiple gene alterations.


OBJECTIVE
The aim of the study is to investigate the relationship among cytoplasmatic COX-1 and COX-2, Bcl-2 and nuclear P53 in chronic gastritis, metaplasia, and intestinal and gastric cancer.


METHODS
COX-1, COX-2, P53, and Bcl-2 were evaluated by immunohistochemistry in 34 gastric adenocarcinoma (GA) tissues obtained from gastric resection, 21 tissues of patients with chronic gastritis (CG), and 34 with intestinal metaplasia (IM) obtained from endoscopic biopsies.


RESULTS
COX-1 and COX-2 were expressed in more than 85% of the tissues. A correlation between COX-1 and COX-2 were observed (r = 0.66). P53 was positive in 29% CG, 20% of IM and in 59 % of GA. Bcl-2 was negative in all the CG, in 88% of IM, and in 85% of GA. P53 staining was expressed more frequently in gastric cancer when compared to CG (p = 0.05) or IM (p = 0.003). The expression of Bcl-2 was also higher in gastric cancer (p = 0.002) and in intestinal metaplasia (p = 0.04) when compared to CG. There were no difference between metaplasia and chronic gastritis for P53 or Bcl-2. The immunoreactivity of COX-2 in gastric cancer was higher in the intestinal type (58%) than in diffuse type. A higher expression of COX-2 was found in advanced gastric cancer (p = 0.019). P53 was also more frequent in node positive cancer (p = 0.04).


CONCLUSIONS
COX-2 is probably involved in gastric carcinogenesis, being an early alteration in cancer. Although we observed in this study a correlation between COX-2 and depth of cancer, this association as a prognostic marker is not well defined. P53 and Bcl-2 was expressed mainly in gastric cancer, being probably a latest alteration in gastric development.
Forones
Nora Manoukian
NM
Oncology Group/Gastroenterology Division, Pathology Department, Universidade Federal de Sao Paulo (UNIFESP/EPM), Sao Paulo, Sao Paulo, Brazil. nora@gastro.epm.br
Kawamura
Kharen Yaemi
KY
Segreto
Helena Regina Comodo
HR
Artigiani Neto
Ricardo
R
Focchi
Gustavo Rubino de Azevedo
GR
Oshima
Celina Tizuko Fujiyama
CT
D000328:Adult; D000368:Aged; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000201:enzymology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human