Differences in oxidative stress dependence between gastric adenocarcinoma subtypes.
OBJECTIVE
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).


CONCLUSIONS
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.
Bancel
Brigitte
B
Hopital de la Croix-Rousse, Department of Pathology, 103 Grande-Rue de la Croix-Rousse, 69004 Lyon, France. brigitte.bancel@chu-lyon.fr
Esteve
Jacques
J
Souquet
Jean-Christophe
JC
Toyokuni
Shinya
S
Ohshima
Hiroshi
H
Pignatelli
Brigitte
B
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002278:Carcinoma in Situ / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D011230:Precancerous Conditions / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D015415:Biomarkers; D004273:DNA, Neoplasm; D003848:Deoxyguanine Nucleotides; D009363:Neoplasm Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II