Atrophy and altered mesenchymal-epithelial signaling preceding gastric cancer

Chronic inflammation in the stomach (gastritis) induces gastric atrophy characterized by the loss of the acid-secreting oxyntic glands. Although the initial report of phenotypic changes that precede gastric cancer suggest that these steps occur sequentially (Correa et al. 1975), whether atrophy precedes metaplasia or occurs concurrently is unclear. Nevertheless, the metaplastic cell that begins to repopulate the gastric epithelium under hypochlorhydric conditions is a mucous cell of gastric or intestinal origin (Goldenring and Nomura 2006; Kang et al. 2005; Nomura et al. 2004; Oshima et al. 2006). Although Helicobacter pylori infection is the major reason chronic inflammation develops in the stomach, the molecular networks linking chronic inflammation to the atrophic/metaplastic changes are not well understood. This chapter reviews the causes of gastric atrophy and highlights the role that some activated signaling pathways have in committing the mucosa to neoplastic transformation.