Gastric Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 21, 2006; 12(7): 1005-1012
Published online Feb 21, 2006. doi: 10.3748/wjg.v12.i7.1005
Differences in oxidative stress dependence between gastric adenocarcinoma subtypes
Brigitte Bancel, Jacques Estève, Jean-Christophe Souquet, Shinya Toyokuni, Hiroshi Ohshima, Brigitte Pignatelli
Brigitte Bancel, Hôpital de la Croix-Rousse, Department of Pathology, Lyon, France
Jacques Estève, Centre Hospitalier Lyon-Sud, Department of Biostatistics, Pierre-Bénite, France
Jean-Christophe Souquet, Hôpital de la Croix-Rousse, Department of Gastroenterology, Lyon, France
Shinya Toyokuni, Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Hiroshi Ohshima, Brigitte Pignatelli, International Agency for Research on Cancer, Endogenous Risk Factors Group, Lyon, France
Brigitte Pignatelli, Clinical Epidemiology Unit, Department of Medical Information, Hospices Civils de Lyon, France
Correspondence to: Dr. Brigitte Bancel, Hôpital de la Croix-Rousse, Department of Pathology, 103 Grande-Rue de la Croix-Rousse, 69004 Lyon, France.
Telephone: +33-4-72071877 Fax: +33-4-72071879
Received: March 22, 2005
Revised: July 2, 2005
Accepted: July 20, 2005
Published online: February 21, 2006

AIM: To investigate the extent of oxidative stress in pre-neoplastic and neoplastic gastric mucosa in relation to their pathological criteria and histological subtypes.

METHODS: A total of 104 gastric adenocarcinomas from 98 patients (88 infiltrative and 16 intraepithelial tumors) were assessed immunohistochemically for expression of iNOS and occurrence of nitrotyrosine (NTYR)-containing proteins and 8-hydroxy-2’-deoxyguanosine (8-OH-dG)-containing DNA, as markers of NO production and damages to protein and DNA.

RESULTS: Tumor cells staining for iNOS, NTYR and 8-OH-dG were detected in 41%, 62% and 50% of infiltrative carcinoma, respectively. The three markers were shown for the first time in intraepithelial carcinoma. The expression of iNOS was significantly more frequent in tubular carcinoma (TC) compared to diffuse carcinoma (DC) (54% vs 18%; P = 0.008) or in polymorphous carcinoma (PolyC) (54% vs 21%; P = 0.04). NTYR staining was obviously more often found in TC than that in PolyC (72% vs 30%; P=0.03). There was a tendency towards a higher rate of iNOS staining when distant metastasis (pM) was present. In infiltrative TC, the presence of oxidative stress markers was not significantly correlated with histological grade, density of inflammation, the depth of infiltration (pT), lymph nodes dissemination (pN) and pathological stages (pTNM).

CONCLUSION: The iNOS-oxidative pathway may play an important role in TC, but moderately in PolyC and DC. DNA oxidation and protein nitration occur in the three subtypes. Based on the significant differences of NTYR levels, TC and PolyC appear as two distinct subtypes.

Keywords: Gastric neoplasms, Nitric oxide synthase, H pylori, Nitrotyrosine, 8-hydroxydeoxyguanosine, Oxidative stress