Helicobacter pylori infection generated gastric cancer through p53-Rb tumor-suppressor system mutation and telomerase reactivation.
OBJECTIVE
To investigate the relationship between Helicobacter pylori (H.pylori) infection and the expressions of the p53, Rb, c-myc, bcl-2 and hTERT mRNA in a series of diseases from chronic gastritis (CG), intestinal metaplasia type I or II(IMI-II), intestinal metaplasia type III (IMIII), mild or modest dysplasia (DysI-II), severe dysplasia (DysIII) to gastric cancer(GC) and to elucidate the mechanism of gastric carcinogenesis relating to H.pylori infection.


METHODS
272 cases between 1998 and 2001 were available for the study including 42 cases of CG, 46 cases of IMI-II, 25 cases of IMIII, 48 cases of DysI-II, 27 cases of DysIII, 84 cases of GC. H.pylori infection and the expressions of p53, Rb, c-myc, bcl-2 were detected by means of streptavidin-peroxidase (SP) immunohistochemical method. HTERT mRNA was detected by in situ hybridization (ISH).


RESULTS
The expressions of p53, Rb, c-myc, hTERT mRNA and bcl-2 were higher in the GC than in CG, IM, Dys. The expression of c-myc was higher in IMIII with H.pylori infection (10/16) than that without infection (1/9) and the positive rate in DysI-II and DysIII with H.pylori infection was 18/30 and 13/17, respectively, higher than that without infection (4/18 and 3/10, respectively). In our experiment mutated p53 had no association with H.pylori infection, the expression of Rb was associated with H.pylori infection in GC, but the p53-Rb tumor-suppressor system abnormal in DysI-II cases, DysIII and GC cases with H.pylori infection was 21/30, 15/17 and 48/48 respectively, higher than non-infection groups (4/18, 3/10, 28/36). Furthermore the level of hTERT mRNA in GC with H.pylori infection (47/48) was higher than that without infection (30/36), however the relationship between bcl-2 and H.pylori was only in IMIII. C-myc had a close association with hTERT mRNA in DysIII and GC (P=0.0 253,0.0 305 respectively).


CONCLUSIONS
In the gastric carcinogenesis, H.pylori might cause the severe imbalance of proliferation and apoptosis in the precancerous lesions (IMIII and GysIII) first, leading to p53-Rb tumor-suppressor system mutation and telomerase reactivation, and finally causes gastric cancer.
Lan
Jing
J
Department of Pathology, Zhongnan Hospital, Wuhan University,Wuhan city 430071, Hubei Province, China. lanjing_2002@hotmail.com
Xiong
Yong-Yan
YY
Lin
Yi-Xian
YX
Wang
Bi-Cheng
BC
Gong
Ling-Ling
LL
Xu
Hui-Sen
HS
Guo
Guang-Song
GS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D005260:Female; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D016481:Helicobacter Infections / Q000235:genetics / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D012189:Retrospective Studies; D013270:Stomach / Q000473:pathology; D013272:Stomach Diseases / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019098:Telomerase