Moss S F, Sordillo E M, Abdalla A M, Makarov V, Hanzely Z, Perez-Perez G I, Blaser M J, Holt P R
Department of Medicine, St. Luke's-Roosevelt Hospital Center, New York, New York 10025, USA.
Cancer Res. 2001 Feb 15;61(4):1406-11.
Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated "blindly" using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization.
幽门螺杆菌在胃内定植是发生非贲门部胃癌的一个危险因素。幽门螺杆菌与癌症之间的关联可能归因于上皮细胞更新增加，这可能与抗胃抗体有关。之前的两项研究报告称，在表达与毒力相关的cagA基因的幽门螺杆菌菌株感染的患者中，增殖相对于凋亡出现不成比例的增加。这导致了一种假说，即cagA阳性菌株导致的凋亡缺失可能促进肿瘤形成。因此，我们在一项大型前瞻性研究中，研究了幽门螺杆菌对胃上皮增殖、凋亡以及血清抗壁细胞抗体存在情况的影响。使用经过验证的免疫组织化学方法，对60例非溃疡性消化不良患者的两块胃窦活检组织和两块胃体活检组织进行“盲法”评估增殖和凋亡情况，并将结果与血清抗壁细胞抗体的存在情况相关联。通过组织学、活检尿素酶试验和血清学评估幽门螺杆菌定植情况。幽门螺杆菌阳性患者的胃窦和胃体增殖均增加了2倍，与幽门螺杆菌cagA状态无关，且与组织学胃炎呈正相关。仅在感染cagA阳性幽门螺杆菌菌株的患者中，胃窦和胃体的凋亡增加。抗壁细胞抗体在幽门螺杆菌定植患者中并不更常见，其存在与上皮凋亡评分呈负相关。因此我们得出结论，在非溃疡性消化不良患者中，携带幽门螺杆菌与增殖增加有关。此外，cag致病岛与凋亡增加有关。我们的结果不支持这样的假说，即与携带cagA阳性菌株相关的胃上皮细胞凋亡相对不足。在决定幽门螺杆菌定植的长期结果方面，宿主因素可能比细菌产物更重要。
