The natural history of intraepithelial neoplasia: relevance to the search for intermediate endpoint biomarkers.
The development of carcinomas, defined as invasive epithelial neoplasms, is preceded by a preinvasive stage termed intraepithelial neoplasia that typically lasts for years. Intraepithelial neoplasia is the target tissue for the action of chemopreventive agents and the site where biomarkers frequently develop. The term "dysplasia" refers to the morphological alterations that characterize intraepithelial neoplasia and, according to many authors, consists of seven basic changes that are the same for the majority of epithelia. These are increased nuclear size, abnormal nuclear shape, increased nuclear stain uptake, nuclear pleomorphism (increased variation in size, shape, and stain uptake), increased mitoses, abnormal mitoses, and disordered or absent differentiation. Clonal evolution appears to begin early in the neoplastic process during intraepithelial neoplasia. The use of intraepithelial neoplasia as an intermediate endpoint biomarker requires that effective chemopreventive agents cause it to regress. Two examples are the regression of dysplastic oral leukoplakia produced by beta-carotene and the regression of colonic polyps in familial polyposis patients following treatment with the nonsteroidal antiinflammatory drug sulindac. There is a critical need to identify and develop biomarkers that correlate with the appearance and regression of intraepithelial neoplasia.
Boone
C W
CW
Chemoprevention Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Kelloff
G J
GJ
Steele
V E
VE
D015415:Biomarkers / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology* / Q000503:physiopathology*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000648:ultrastructure; D006801:Humans; D008938:Mitosis; D011230:Precancerous Conditions / Q000473:pathology*
D015415:Biomarkers