Premalignant lesions in gastric cancer
ABSTRACT Despite a plateau in incidence, gastric cancer is one of the most common cancers worldwide and causes considerable morbidity
and mortality. Premalignant gastric lesions are well known risk factors for the development of intestinal-type gastric adenocarcinomas.
In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic
gastritis, intestinal metaplasia, and adenoma/dysplasia to gastric carcinoma. This progression is paralleled by a stepwise
accumulation of multiple genetic and epigenetic abnormalities. Detection, treatment, and molecular analyses of premalignant
lesions may thus provide a basis for gastric cancer prevention. This review describes an overview of current knowledge on
premalignant gastric lesions. It also reviews the issue of surveillance of patients with premalignant lesions in order to
improve the survival of patients with gastric cancer.
Pathologica 11/2003; 95(5):281.
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ABSTRACT: A large proportion of patients attending open access endoscopy have histological and gross pathological findings that are potentially premalignant. The proportion of these patients who go on to develop malignancies and the timescale over which this occurs are uncertain. This study aims to discover the incidence of gastric cancers in this "high risk" group and to examine the potential for their early diagnosis and treatment. A total of 1753 patients attended open access endoscopy. From these, 166 patients with dysplasia, intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy were studied. Patients were endoscoped annually. Additionally, patients with ulcers were re-examined at two monthly intervals until ulcer healing. Cancers detected were treated by gastrectomy. Twenty two of 1753 patients attending open access endoscopy had gastric cancer (1.3%). In the study population, 14 cancers were detected over 10 years (8.4 %). These were of an earlier stage than those detected at open access (stage I and II 67% v 23%; p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%. In patients with atrophic gastritis or intestinal metaplasia, annual surveillance can detect most new tumours at an early stage with a major improvement in survival. Potential benefits of such a surveillance programme are large and warrant further investigation in a multicentre randomised controlled trial.Gut 04/2002; 50(3):378-81. · 13.32 Impact Factor
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ABSTRACT: It is generally known that replication errors (RERs) at microsatellite loci detected in human malignancies reflect a genetic instability that is caused by abnormalities of DNA mismatch repair system and underlie human carcinogenesis. The authors analyzed RERs in precancerous lesions and adenocarcinomas of the stomach to learn when genetic instability occurs in stomach carcinogenesis. In addition, the authors examined genetic instability occurs in stomach carcinogenesis. In addition, the authors examined genetic alterations of the p53 and adenomatous polyposis coli (APC) genes to investigate the correlation between genetic instability and genetic alterations in these tumor suppressor genes. The authors examined microsatellite assay at 9 microsatellite loci in 24 sporadic gastric cancers, 12 gastric adenomas, and 9 intestinal metaplasia mucosae of the stomach from patients with gastric cancers using fresh frozen or formalin fixed and paraffin embedded samples paired with normal mucosae. They also screened loss of heterozygosity (LOH) of the p53 and APC genes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. In total, the RER(+) phenotypes were observed in 8 of 24 (33%) gastric cancers, 5 of 12 (42%) gastric adenomas, and 3 of 9 (33%) intestinal metaplasia mucosae of the stomach. Histology, RERs were detected in 3 of 9 (33%) well differentiated adenocarcinomas, 2 of 11 (18%) poorly differentiated adenocarcinomas, and 3 of 4 (75%) scirrhous type gastric cancers respectively. Several cases showed RERs at many microsatellite loci simultaneously. Some RER(+) phenotypes had genetic alterations of the p53 or APC genes detected by LOH using PCR-RFLP analysis. However, no significant correlation was found between RER(+) phenotypes and LOH in these genes. The frequency of RERs in detected gastric cancers were almost the same when compared with previously reported data. Interestingly, RERs were detected in greater than 30% of precancerous lesions, suggesting that genetic instability is an early somatic event of multistep stomach carcinogenesis. It also suggests that the adenoma-carcinoma sequence does exist in stomach carcinogenesis, especially in well differentiated adenocarcinomas. Moreover, alterations in the p53 and APC genes detected by PCR-RFLP analysis did not correlate with RER(+) phenotypes.Cancer 04/1996; 77(8 Suppl):1620-7. DOI:10.1002/(SICI)1097-0142(19960415)77:8<1620::AID-CNCR30>3.0.CO;2-# · 4.90 Impact Factor