Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 15, 2000; 6(6): 848-854
Published online Dec 15, 2000. doi: 10.3748/wjg.v6.i6.848
Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions: H. pylori infection, histological types and staging
Heng Jun Gao, Lian Zhen Yu, Jian Feng Bai, Yan Shen Peng, Gu Sun, Han Lin Zhao, Kun Miu, Xiu Zhen Lü, Xiao Yong Zhang, Zhi Quan Zhao
Heng Jun Gao, Lian Zhen Yu, Kun Miu, Xiu Zhen Lü, Xiao Yong Zhang, Zhi Quan Zhao, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Jian Feng Bai, Gu Sun, Han Lin Zhao, Department of Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Yan Shen Peng, Renji Hospital, Shanghai Second Medical University, Shanghai Institute of Digestive Disease, Shanghai 200001, China
Heng Jun Gao, graduated from Yangzhou Medical College in 1986, worked in Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University as an assistant professor and a resident physician, now Ph.D. candidate in Renji Hospital, Shanghai Second Medical University, Shanghai Institute of Digestive Disease, majoring in the relationship between Helicobacter pylori and gastric cancer and gene therapy of gastrointestinal cancer, having 24 papers published, being the chief editor of two books and principal investigator for the study of two projects.
Author contributions: All authors contributed equally to the work.
Correspondence to: Heng Jun Gao, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China. Email: GaoHengJun@163.net
Telephone: 0086-21-63260930 Ext.2134
Received: April 3, 2000
Revised: April 12, 2000
Accepted: April 19, 2000
Published online: December 15, 2000
Abstract

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.

Keywords: stomach neoplasms; gastric mucosa/injuries; precancerous conditions; gene expression; Helicobacter pylori; gastroscopy; immunohistochemistry; neoplasm staging