Despite a global decline in the incidence of gastric cancer over the past 3 decades, it remains the fifth most commonly diagnosed cancer and the third most common cause of cancer deaths worldwide.1 In the United States it is the fourth most commonly diagnosed GI malignancy, after colorectal, pancreas, and liver cancer. The prevalence remains high in Latin America and Asia, which has implications in the United States because of growing Hispanic and Asian populations.2,3 In recent years, a change in the trend of gastric cancer among non-Hispanic whites has been observed, particularly in women younger than 50 years old.45
Gastric adenocarcinomas are classified into two subcategories based on location (cardia and noncardia) and histology (intestinal and diffuse types).6,7 Atrophic gastritis and gastric intestinal metaplasia (GIM) are considered precursors of intestinal-type noncardia gastric adenocarcinoma. The Correa cascade is a commonly accepted precancer sequence for noncardia gastric adenocarcinoma that describes mucosal changes from inflammation to atrophy to metaplasia to intraepithelial neoplasia and culminating in carcinoma.8,9 It has been observed that GIM may be the histologic change prior to the development of dysplasia and over 50% of patients with high-grade dysplasia will progress to adenocarcinoma.10-12 In the United States, GIM has the highest prevalence in African Americans, Hispanics, and East Asians, with the overall GIM prevalence regardless of ethnicity reported from 3.05% to 19.2%.5,13
Risk factors and subclassification
Replacement of the foveolar and/or glandular epithelium in the oxyntic and antral mucosa by intestinal epithelium results in GIM. It can be focal when limited to one region of the stomach or extensive when two or more regions are involved.14 The main risk factors for GIM development are Helicobacter pylori infection, tobacco, alcohol consumption, high salt intake, and chronic bile reflux.15,16 Additional risks for developing gastric cancer include older age, certain ethnicities, and male sex.17
CagA strains of H. pylori can promote carcinogenesis by inducing a mitogenic cellular response and downregulating cell adhesion.18,19 Less carcinogenic risk is associated with H. pylori Cag-A negative strains; however, they also have oncogenic potential mediated by expression of babA2 and vacA genes.20 Hence, the combination of multiple virulent factors encoded in babA2, CagA, and vacA genes has been associated with increased risk of GIM, inflammation, and development of gastric cancer.15 The clinical usefulness of genotyping H. pylori strains specifically to survey precancerous gastric lesions remains to be seen because of a lack of sufficient clinical studies. In addition, genotyping H. pylori is not commonly performed as part of clinical practice.
The loss of parietal cells seen in atrophic gastritis due to chronic H. pylori infection has been linked to the development of metaplasia due to possible loss of differentiation-promoting factors. As a result, metaplastic cells emerge that express spasmolytic polypeptide (SP or TFF2); hence, this type of metaplasia is referred to as spasmolytic polypeptide–expressing metaplasia (SPEM). The cellular mechanism that may explain a precursor role of SPEM in the development of GIM remains unknown.14 A second competing theory for the development of GIM is the clonal expansion of stem cells in the gastric isthmus that can lead to dysplasia and cancer development.14
On the basis of histological similarities with small intestinal or colonic epithelium, GIM can be further classified into complete or incomplete intestinal metaplasia.21 Complete intestinal metaplasia most closely resembles small intestinal epithelium with a brush border and goblet cells. Incomplete intestinal metaplasia resembles the colonic epithelium and lacks a brush border. A second classification further classifies GIM into three subtypes: Type I contains nonsecretory absorptive cells and sialomucin secreting goblet cells; type II has few absorptive cells, columnar cells secreting sialomucin, goblet cells secreting mainly sialomucin but some sulphomucin, and presence of Paneth cells; and type III consists of columnar cells secreting predominantly sulphomucin, goblet cells secreting sialomucin or sulphomucin, and absence of Paneth cells.15,22 In this subclassification, type I GIM is known as complete GIM and types II and III as incomplete GIM.23-25
Multiple studies performed outside of the United States have shown a higher progression risk to gastric adenocarcinoma in incomplete intestinal metaplasia, or type III intestinal metaplasia.26-32 Also, the risk of gastric cancer has been demonstrated to be higher among patients with a greater area of metaplasia and extensive intestinal metaplasia, defined as GIM in both the antrum and corpus.33,34 Hence, the extent of the metaplasia determined with mapping biopsies, regardless of the subtype, should also be incorporated into the risk assessment of the patient. Currently, a major limitation in the United States is a standardized method of pathologic reporting including subclassification of incomplete versus complete intestinal metaplasia.