Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions: H. pylori infection histological types and staging

摘要

AIM: To investigate the expression of multiple genes and the behavior of cellular biology in gastric cancer (GC) and other gastric mucosal lesions and their relations to Helicobacter pylori (H. pylori) infection, tumor staging and histological subtypes.METHODS: Three hundred and twenty-seven specimens of gastric mucosa obtained via endoscopy or surgical resection, and ABC immunohistochemical staining were used to detect the expression of p53, p16, Bcl-2 and COX-2 proteins. H. pylori was determined by rapid urea test combined with pathological staining or ¹⁴C urea breath test. Cellular image analysis was performed in 66 patients with intestinal metaplasia (IM) and/or dysplasia (Dys). In 30 of them, both cancer and the paracancerous tissues were obtained at the time of surgery. Histological pattern, tumor staging, lymph node metastasis, grading of differentiation and other clinical data were studied in the medical records.RESULTS: p16 expression of IM or Dys was significantly lower in positive H. pylori chronic atrophic gastritis (CAG) than those with negative H. pylori (CAG: 54.8% vs 88.0%, IM:34.4% vs 69.6%, Dys: 23.8% vs 53.6%, all P < 0.05), Bcl-2 or COX-2 expression of IM or Dys in positive H. pylori cases was significantly higher than that without H. pylori (Bcl-2: 68.8% vs 23.9%, 90.5% vs 60.7%; COX-2: 50.0% vs 10.8%, 61.8% vs 17.8%; all P < 0.05). The mean number of most parameters of cellular image analysis in positive H. pylori group was significantly higher than that in negative H. pylori group (Ellipser: 53 ± 14, 40 ± 12 μm, Area 1: 748 ± 572, 302 ± 202 μm², Area-2: 3050 ± 1661, 1681 ± 1990 μm², all P < 0.05; Ellipseb: 79 ± 23, 58 ± 15 μm, Ratio 1: 22% ± 5%, 13% ± 4%, Ratio-2: 79% ± 17%, 53% ± 20%, all P < 0.01). There was significant correlation between Bcl-2 and histologic pattern of gas tric carcinoma, and between COX-2 and tumor staging or lymph node metastasis (Bcl-2: 75.0% vs 16.7%; COX-2: 76.0% vs 20.0%, 79.2% vs 16.7%; all P < 0.05).CONCLUSION: p16, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infection. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.