Field defects in progression to adenocarcinoma of the colon and esophagus

Abstract

A field of defective tissue (field defect) appears to be an early stage in the progression to adenocarcinoma of both the colon and the esophagus. In both cases the field is comprised of cells characterized by resistance to induction of apoptosis, aberrant increased proliferation and genomic instability. Specific mutations and epimutations occur in both types of field. Also there is evidence for aberrant overexpression or underexpression of specific proteins. Most of these early molecular alterations appear to promote either enhanced apoptosis resistance, proliferation, or genomic instability. The molecular alterations that are present early are often, but not always, also present to an even greater degree in the cancer itself. Many of the important events in the development of colonic and esophageal adenocarcinoma first occur in tissues that are histologically neither dysplastic nor malignant. The identification of early molecular defects in morphologically normal appearing tissue is paramount in identifying subjects at high risk for cancer.