不同病变胃组织端粒酶活性及其与幽门螺杆菌感染的关系

The Relationship between Telomerase Activity and Helicobacter pylori Infection in Various Pathological Gastric Mucosal Lesions

分析不同病变胃粘膜端粒酶活性的差异及其与幽门螺杆菌（H．pylori）感染的关系，探讨端粒酶活性、H.pylori感染与胃粘膜癌变的关系。方法：应用瑞粒重复扩增法测定正常胃粘膜、癌前病变和胃癌组织中的端粒酶活性，用酶免疫法检测H.Pylori感染患者的血清H．Pylori-CagA-IgG水平，并分析端粒酶活性与H.Pylori-CagAriIgG水平的关系。结果：172例胃镜活检标本中，正常胃粘膜、浅表性胃炎、慢性萎缩性胃炎无肠化、伴1度、2度肠化和胃癌组织的端粒酶阳性率分别为0％、0％、25％、37．5％和88．89％。45例手术切除的胃癌组织和相应的非癌胃组织也呈相似结果。正常胃粘膜、浅表性胃炎、慢性萎缩性胃炎无肠化及伴1度、2度肠化组织的H．pylori阳性率分别为0％、52.17％、60％、70％和75％。45例手术切除胃癌的非癌胃组织无肠化、伴1度、2度肠化的H．pylori感染强度分别为10．8±9．6个／50腺体、41．3±31．1个／50腺体和86．4±47．8个／50腺体。慢性浅表性胃炎患者的H、pylori-CagA-IgG抗体水平显著低于胃癌患者（P＜0.01），22例HPylori阳性胃癌患者感染的HPylori全部为cagA阳性菌株，其非癌胃粘膜有12例呈现端粒酶活性（54．55％）；相反H.pylori阳性的22例慢性浅表性胃炎患者感染的H.Pylori只有8例为cagA阳?

Background/Aims: To analyze the telomerase activity implicated in Helicobacter pylori (H. pylori)infection and to evaluate the relation of telomerase activity and H. pylori infection to gastric carcinomatous changes. Methods: Telomerase activity was detected by telomere repeated amplification protocol (TRAP) in normal gastric mucosa, precancerous lesions and gastric carcinoma. Serum H. pylori-CagA-IgG antibody was determined by enzyme immunoassay in H. pylori infected patients. The relationship between telomerase activity and H. pylori-CagA-IgG antibody was studied by matched method using 22 pairs of H. pylori-positive patients including non-neoplastic mucosa surrounding the gastric cancer and that from chronic superficial gastritis (CSG). Results: The TRAP assay revealed that all normal gastric and CSG mucosa were negative for telomerase acitvity. In chronic atrophic gastritis (CAG), the positivity rates of telomerase activity of non-metaplasia, intestinal metaplasia (IM) of grade 1 and 2 were 0%, 25% and 37.5%, respectively. 16 out of l8 gastric carcinomas showed telomerase activity, and their positivity rate was the highest (88.89%). Among the 45 resected gastric specimens, the cancerous tissue and the surrounding non-neoplastic gastric mucosa showed similar results,39 out of 45 tumor revealed telomerase activity (86.67%). The positivity rates of telomerase activity of non-IM, IM grade 1 and 2 in the surrounding nontumorous tissues were 0%, 31.82% and 100%, respectively. The incidence in IM grade 2 or tumor specimens was significantly higher than that in non-IM or IM grade 1 (P< 0.01). In all biopsy specimens, the H. pylori positivity rates in normal gastric mucosa,CSG, non-IM, IM grade 1 and 2 CAG were 0%, 52.17%, 60%, 70% and 75%, respectively. In 45 resected gastric carcinoma, the surrounding nontumorous tissue showed similar results. This study also showed that H. pylori-CagA-IgG antibody was significantly lower in patients with CSG than that in patients with gastric carcinoma (P<0.01). All 22 H. Pylori-positive patients with gastric carcinoma were infected with cagA+ strain (100%), 12 of the 22 surrounding nontumorous gastric mucosa specimens were found to have positive telomerase activity (54.55%). In contrast. only 8 of 22 H. pylori-positive CSG were infected with cagA+ strain (36.36%); all of the 22 gastric mucosa showed negative telomerase activity. Conclusions: The normal and CSG mucosa express no telomerase activity. Telomerase activity in CAG increases as the grade of IM progresses. Whereas the telomerase activity of gastric carcinomatous mucosa ranks the highest. The degree of H. pylori infection increases with progress of telomerase activity in non-cancerous mucosa surrounding the gastric cancer, and infected H. pylori is usually cagA+ strain, whereas infected H. pylori in CSG is usually cagA strain. Thus, telomerase activity may serve as a molecular biological marker for diagnosis of early gastric carcinoma. cagA+ H. pylori infection may be a strong triggerring signal for telomerase reactivation.