The two histological main types of gastric carcinoma; diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification

Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority.

The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.

/pdf/comprehensive-molecular-characterization-of-gastric-3jzhmi95fs.pdf

Comprehensive molecular characterization of gastric adenocarcinoma

Background Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. Methods We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. Results Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metap...

Helicobacter pylori infection and the development of gastric cancer

Background. Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case–control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. Methods. From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. Results. The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patient...

https://www.nejm.org/doi/pdf/10.1056/NEJM199110173251603

Helicobacter pylori infection and the risk of gastric carcinoma.

The Cancer Genome Atlas (TCGA) is a public funded project that aims to catalogue and discover major cancer-causing genomic alterations to create a comprehensive "atlas" of cancer genomic profiles. So far, TCGA researchers have analysed large cohorts of over 30 human tumours through large-scale genome sequencing and integrated multi-dimensional analyses. Studies of individual cancer types, as well as comprehensive pan-cancer analyses have extended current knowledge of tumorigenesis. A major goal of the project was to provide publicly available datasets to help improve diagnostic methods, treatment standards, and finally to prevent cancer. This review discusses the current status of TCGA Research Network structure, purpose, and achievements.

https://www.termedia.pl/Journal/-77/pdf-24047-10?filename=The Cancer Genome Atlas.pdf

The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge.

On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer

The incidence of gastric cancer has declined markedly in Finland during the last 4 decades. To document the changes caused by that in the ratio of the intestinal type (IT) to the diffuse type (DT) of gastric carcinoma we compared the 367 cases diagnosed from southwestern Finland at the Department of Pathology, Turku University, from 1950-1959 and 1076 cases from 1980-1989. IT virtually disappeared in the male and female populations younger than 50 years, and in patients younger than 60 years, DT became more common than IT (P < 0.001). The transitional age, the time at which IT exceeds DT in frequency, shifted by 20 years to older age groups. In patients older than 60 years, IT remained the dominant type, but the ratio of IT to DT (IT:DT) decreased in men from 3.8 to 2.1 (P < 0.05) and in women from 4.4 to 2.1 (P < 0.001). No decrease in the frequency of DT could be demonstrated in the material studied. The disappearance of the male-dominant IT in the younger male population changed the male-to-female ratio of patients reported to the Finnish Cancer Registry. When the ratio IT:DT in Finland was compared with the ratios reported by the authors in data from other continents and by other investigators, regional variations in basal level of IT:DT emerged. This phenomenon seems to be based on the differing genetic susceptibility to DT of various races. The decrease of IT, seen in reports from regions with declining incidence of gastric carcinoma, seems to be connected to a diminished rate of severe chronic gastritis.

Epidemiology of intestinal and diffuse types of gastric carcinoma : a time-trend study in Finland with comparison between studies from high- and low-risk areas

A total of 305 total or proximal gastrectomies for gastric carcinoma were performed in 291 patients. Of the tumors 51.5% were of the intestinal-type and 35.7% were of the diffuse-type of carcinoma. Proximal gastrectomy was performed in 68 patients, total gastrectomy in 230, and anastomotic resection in 7. In 25 patients a reresection for recurrent carcinoma was performed. After total gastrectomy the main reconstructive procedures were end-to-side esophago-jejunostomy and Roux-en-Y esophagojejunostomy. The hospital mortality rate was 13.4%. The main causes of death were anastomotic leakage and pulmonary embolism. The incidence of leakage was 10.8% and the complication proved fatal in 36.4% of the patients who developed it. After Roux-en-Y reconstruction only 8% of the patients with leakage died. After curative operations 27% of the patients survived for over 5 years (relative survival rate of 33%). The 5-year survival rates for the intestinal-type and diffusetype of carcinoma were similar, but the 10-year survival rate for intestinal-type of carcinoma was significantly better. In our view a relatively high mortality rate after total or proximal gastrectomy has to be accepted when older patients are concerned, and when no other curative procedure is possible on account of the site and extent of invasion of the tumor. However, in cases where radical resection can be achieved by means of subtotal gastrectomy, this method is best. At present, in cases of the diffuse-type of carcinoma of the corpus, we perform a total gastrectomy instead of subtotal gastrectomy. In the small series of reresections the results were encouraging.

Total and proximal gastrectomy in the treatment of gastric carcinoma: A series of 305 cases

Gastric glandular tumors provided with excretory ducts, and criticism of the theory of the tumors arising in heterotopic pancreas; observations on the occurrence of atypical glands in the stomach.

Pekka A. Laurén

Papers

The two histological main types of gastric carcinoma; diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification

On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer

Epidemiology of intestinal and diffuse types of gastric carcinoma : a time-trend study in Finland with comparison between studies from high- and low-risk areas

Total and proximal gastrectomy in the treatment of gastric carcinoma: A series of 305 cases

Gastric glandular tumors provided with excretory ducts, and criticism of the theory of the tumors arising in heterotopic pancreas; observations on the occurrence of atypical glands in the stomach.