Development and growth of normal; metaplastic and dysplastic oesophageal mucosa

Abstract

The past 40 years has seen the development of molecular cell biology and its application to the pathophysiology of human disease. The mechanisms which control the proliferation and differentiation of cells, as well as the failure of these processes, are fundamental to most diseases. These topics are well illustrated by diseases of the oesophagus which present an instructive spectrum of pathological changes including benign inflammation, three types of metaplasia, dysplastic changes and two common types of cancer (adenocarcinoma and squamous cell carcinoma). Recent study of the oesophageal mucosa has provided insight into the many processes required for normal development as well as their complex interactions. The processes are usually effective in maintaining the integrity of the oesophageal epithelium in the face of even severe injury. However, under conditions of severe, prolonged exposure to noxious agents (such as gastric juice, duodenal contents or therapeutic drugs), disorders of proliferation result in metaplasia and dysplasia of the oesophageal mucosa. The progressive failure of normal growth controls depends on the disruption of many negative feedback mechanisms, resulting ultimately in the development of a clone or clones of cells with autonomous proliferative potential and the progression to cancer in the final stages. This review seeks to provide an outline of some of the aspects of oesophageal pathophysiology relating to recent developments of these topics.