Premalignant lesions in gastric cancer

Clinical Journal of Gastroenterology 3(1):6-12. DOI: 10.1007/s12328-009-0130-8

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.

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    ABSTRACT: The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinogenesis is a multistep phenomenon, beginning with precancerous conditions. Among these, adenoma is a direct precursor, because of the dysplastic nature of its cells. However, gastric adenoma is relatively rare. Chronic atrophic gastritis (CAG) is the most common precancerous condition, in which intestinal metaplasia often occurs. Carcinoma develops in CAG through stages of hyperplasia and dysplasia involving both metaplastic and non-metaplastic glands. Molecular alterations, including replication error and p53 and APC gene mutation and aneuploidy have been found in some of these conditions, confirming their role in carcinogenesis. Carcinomas of the stomach are heterogeneous in cellular composition. Both intestinal and gastric types of cells are found in all types of tumors, indicating the unique characteristics of gastric cancer. Many molecular lesions have been found in gastric carcinomas. Basic changes involve replication errors, telomerase activity, and aberrant CD44 transcripts. Many other changes often show differences in the frequency of their occurrence between the two major histological types of gastric carcinoma: well differentiated versus poorly differentiated, or intestinal type versus diffuse type. The timing and frequency of these changes in the stomach differ from the timing and frequency in colonic carcinogeneis. Pathological evaluation remains reliable and meaningful, in basic research as well as clinical management. To obtain correlation with molecular alterations, the need for detailed pathologic classification of gastric carcinoma is recognized, taking into account its biologic behavior and grades of cell differentiation.The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinomas are unique in their heterogeneity in both cellular composition and molecular changes.
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