|Results 1-1||<< Back|
Mentions: Gastric adenocarcinoma remains the second leading cause of cancer death worldwide, accounting for approximately 10% of all newly diagnosed cancers . It is the most common form of malignant gastric tumor, accounting for about 90% of stomach cancers. Lack of early diagnosis is responsible for the high mortality rates as the disease is usually incurable when diagnosed at an advanced stage with a 5-year survival rate ranging from 5-15% . Clinical outcome is therefore optimized by early stage diagnosis . There is a recognized need to be able to identify and eliminate precursor lesions in order to treat many cancers, and a significant reduction in the mortality rate of GC could be achieved by the implementation of early diagnostic methods. There are two main types of gastric adenocarcinoma according to the Lauren classification defined as intestinal-type and diffuse-type. These histopathological variants have been shown to differ greatly in the phenotypic characteristics at the precursor stage . Intestinal-type carcinomas display obvious glandular differentiation and arise from gastric cells that have undergone IM through a series of histological changes known as the Correa’s Cascade of Gastric Carcinogenesis. Diffuse-type carcinomas are typically poorly differentiated and may arise from either native gastric cells or those that have undergone IM , there are no known defined precursor lesions for this type of cancer [11, 12]. The Lauren classification is widely used as it describes two biological entities that are different in epidemiology, etiology, pathogenesis and behaviour. The Correa’s Cascade of Gastric Carcinogenesis is a model that refers only to intestinal-type carcinoma. The cascade outlines a process of carcinogenesis which is a gradual transition from initial gastritis to diffuse, chronic gastritis, mucosal atrophy, intestinal metaplasia, dysplasia, and finally, carcinoma [1, 13, 14]. The initiation of gastritis in the stomach is often caused by infection with Helicobacter pylori, a bacterial pathogen that frequently colonizes the intestinal mucosa of humans and animals. The organism may be carried asymptomatically for many years; however, it is also a recognized cause of chronic gastritis, gastric ulcers and gastric adenocarcinoma. The evidence linking this pathogen to GC led to H. pylori becoming classified as a class 1 carcinogen by the World Health Organization . Fig. (1) shows a diagrammatic representation of the carcinogenic cascade, this diagram is a modification of the “hypothesis of gastric cancer etiology” as proposed by Correa . Fig. (2) shows the pathology of the key steps along the Correa’s cascade of carcinogenesis. H&E stained paraffin-embedded tissue sections are presented, starting with normal gastric mucosa, Fig. (2a), followed by initial H. pylori-associated gastritis in Fig. (2b) and progression into IM in Fig. (2c), and finally intestinal-type GC in Fig. (2d).
Genetic Mechanisms and Aberrant Gene Expression during the Development of Gastric Intestinal Metaplasia and Adenocarcinoma
Bottom Line: This review aims to highlight the progress to date in the genetic events involved in intestinal-type gastric adenocarcinoma and its precursor lesion, intestinal metaplasia.The use of technologies such as whole genome microarray analysis, immunohistochemical analysis and DNA methylation analysis has allowed an insight into some of the events which occur in intestinal metaplasia and may be involved in carcinogenesis.There is still much that is yet to be discovered surrounding the development of this lesion and how, in many cases, it develops into a state of malignancy.
Affiliation: Department of Clinical Medicine, Trinity College Dublin, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland.
Gastric adenocarcinoma occurs via a sequence of molecular events known as the Correa's Cascade which often progresses over many years. Gastritis, typically caused by infection with the bacterium H. pylori, is the first step of the cascade that results in gastric cancer; however, not all cases of gastritis progress along this carcinogenic route. Despite recent antibiotic intervention of H. pylori infections, gastric adenocarcinoma remains the second most common cause of cancer deaths worldwide. Intestinal metaplasia is the next step along the carcinogenic sequence after gastritis and is considered to be a precursor lesion for gastric cancer; however, not all patients with intestinal metaplasia develop adenocarcinoma and little is known about the molecular and genetic events that trigger the progression of intestinal metaplasia into adenocarcinoma. This review aims to highlight the progress to date in the genetic events involved in intestinal-type gastric adenocarcinoma and its precursor lesion, intestinal metaplasia. The use of technologies such as whole genome microarray analysis, immunohistochemical analysis and DNA methylation analysis has allowed an insight into some of the events which occur in intestinal metaplasia and may be involved in carcinogenesis. There is still much that is yet to be discovered surrounding the development of this lesion and how, in many cases, it develops into a state of malignancy.