Gastric Cancer Of Diffuse Type Research Articles

The normal neuroendocrine cells of the upper gastrointestinal tract lack E-cadherin

Objective. E-cadherin plays a crucial role in the adhesion between epithelial cells and thus epithelial integrity. Moreover, germline mutations in the E-cadherin gene (CDH1) causing loss of E-cadherin function (adhesion) leads to hereditary gastric cancer of the diffuse type, according to Laurén. Even sporadic gastric carcinomas of the diffuse type often lose E-cadherin expression due to mutations. Lack of E-cadherin has been recorded at an early phase in such carcinomas. For 25 years, we have provided evidence for neuroendocrine (NE) cell origin of gastric carcinomas of diffuse type. The present study was, therefore, done to examine whether normal NE cells in the gastrointestinal tract express E-cadherin or not. Methods. During upper gastrointestinal endoscopy, biopsies were taken from normal oxyntic mucosa, gastric carcinoids, gastric carcinomas, and from normal duodenal mucosa. Tissues were examined by immunohistochemistry (IHC) using antibodies toward chromogranin A, synaptophysin, and E-cadherin. Isolated mucosal cells were prepared from biopsies of normal mucosa and examined by antibodies against the same markers by immunofluorescence. Results. Normal gastrointestinal NE cells did not express E-cadherin as assessed by IHC or immunocytochemistry. No expression of E-cadherin was found on tumor cells from gastric carcinoids or cancer of diffuse type examined by IHC. Conclusion. Our findings, which are in contrast to some previous studies, may explain why there is a discrepancy between lack of atypia and malignant biological behavior of such tumors. Since they normally lack the adhesion molecule E-cadherin, reflected in their spread occurrence, only minor changes may result in malignant behavior.

LTA 252GG and GA Genotypes are Associated with Diffuse‐Type Noncardia Gastric Cancer Risk in the Japanese Population

There are limited numbers of reports on the association of lymphotoxin-alpha (LTA) genotypes with gastric cancer. A nested case-control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose. LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3-6.3), p = .01, and RR = 2.7 (95% CI: 1.5-4.8), p < .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2-0.7), p < .001) and never smoking (RR = 0.4 (95% CI: 0.3-0.6), p < .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G-allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7-5.9), p = .009). The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.

Prevalence and prognosis of gastric cancer detected by screening in a large Japanese population: Data from a single institute over 30 years

In Japan, screening examination with photofluorography is widely performed to reduce the mortality due to gastric cancer. The possibility of a future decline in gastric cancer cases and changes in its characteristics is suggested. The aim of this study was to examine the usefulness of direct radiology as a general health screening technique and the historical changes of gastric cancer in Japan. This study involved 936 patients with gastric cancer whose carcinomas were detected by direct radiology as part of a general health screening at the Aichi Prefectural Center for Health Care from 1970 to 2000. We studied the prevalence of gastric carcinoma, its prognosis, differences between the two histological types of carcinoma and historical changes. The age-adjusted cancer detection rate slightly decreased. Comparing two histological types, diffuse-type carcinoma cases relatively increased. Intestinal-type carcinomas increased in the lower portion of the stomach, whereas diffuse-type increased in the upper portion. The 5-year survival rate was 92.7% for intestinal-type carcinoma and 84.8% for diffuse-type. Diffuse-type carcinomas were further progressed than intestinal-type when detected by direct radiology; however, detection of diffuse-type improved, so the percentage of early gastric cancer of diffuse type significantly increased, and the survival rate significantly improved, from 70.4% to 90.5%. The prevalence of gastric cancer has been decreasing, but the proportion of diffuse-type carcinoma localized in the upper portion of the stomach has been increasing in Japan.

Tobacco, alcohol and the risk of gastric cancer by sub‐site and histologic type

Few studies have provided information on the role of smoking and alcohol in the carcinogenesis of gastric cancer by sub-site and histologic type. The relationship of snuff dipping with risk of gastric cancer has also been rarely studied. In a population-based case-control study conducted in 5 counties of Sweden from February 1989 to January 1995, a total of 90 cases of gastric cardia cancer, 260 and 164 cases of distal gastric cancer of intestinal and diffuse types, respectively, and 1164 frequency-matched control subjects were personally interviewed about life-time smoking, use of smokeless tobacco and use of alcohol 20 years ago. Current smokers had a higher risk than never-smokers for all 3 kinds of gastric adenocarcinoma [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.0–3.1 for gastric cardia adenocarcinoma; OR 1.8, 95% CI 1.2–2.7 for distal gastric cancer of intestinal type; and OR 2.2, 95% CI 1.4–3.5 for distal gastric cancer of diffuse type], and the risk rose with increasing dose and duration of smoking among current smokers. However, no elevated risk was observed for ex-smokers. Neither intake of alcoholic beverages nor snuff dipping was associated with an increased risk of any type of cardia or gastric cancer. Our study did not support the hypothesis that the role of tobacco differs by sub-site and histologic sub-type of gastric cancer. Int. J. Cancer 83:223-229, 1999. © 1999 Wiley-Liss, Inc.

Tobacco, alcohol and the risk of gastric cancer by sub-site and histologic type.

Few studies have provided information on the role of smoking and alcohol in the carcinogenesis of gastric cancer by sub-site and histologic type. The relationship of snuff dipping with risk of gastric cancer has also been rarely studied. In a population-based case-control study conducted in 5 counties of Sweden from February 1989 to January 1995, a total of 90 cases of gastric cardia cancer, 260 and 164 cases of distal gastric cancer of intestinal and diffuse types, respectively, and 1164 frequency-matched control subjects were personally interviewed about life-time smoking, use of smokeless tobacco and use of alcohol 20 years ago. Current smokers had a higher risk than never-smokers for all 3 kinds of gastric adenocarcinoma [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.0-3.1 for gastric cardia adenocarcinoma; OR 1.8, 95% CI 1.2-2.7 for distal gastric cancer of intestinal type; and OR 2.2, 95% CI 1.4-3.5 for distal gastric cancer of diffuse type], and the risk rose with increasing dose and duration of smoking among current smokers. However, no elevated risk was observed for ex-smokers. Neither intake of alcoholic beverages nor snuff dipping was associated with an increased risk of any type of cardia or gastric cancer. Our study did not support the hypothesis that the role of tobacco differs by sub-site and histologic sub-type of gastric cancer.