Cw. Boone et al., NATURAL-HISTORY OF INTRAEPITHELIAL NEOPLASIA IN HUMANS WITH IMPLICATIONS FOR CANCER CHEMOPREVENTION STRATEGY, Cancer research, 52(7), 1992, pp. 1651-1659
Intraepithelial neoplasia is of critical importance to the cancer chem
oprevention field because it is a target condition for which drugs mus
t be sought that will prevent its development or stop its progression.
The term "dysplasia" refers to the morphological alterations that cha
racterize intraepithelial neoplasia and according to many authors cons
ists of seven basic morphological changes that occur in the majority o
f human epithelia, as well as in the epithelium of mouse skin papillom
as induced by 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylpho
rbol-13-acetate: increased nuclear size; altered nuclear shape; increa
sed nuclear stain uptake; nuclear pleomorphism (increased variation in
nuclear size, shape, and stain uptake); increased mitoses; abnormal m
itoses; and disordered or absent maturation. Clonal evolution appears
to begin early in the neoplastic process during intraepithelial neopla
sia. Aneuploidy has been found during intraepithelial neoplasia in man
y human epithelia, and, in association with other forms of genetic ins
tability, may provide the increase in genetically variant cells requir
ed for clonal evolution to occur. It is postulated that two major fact
ors affecting the rate of progression of intraepithelial neoplasia are
the cellular mutation rate, which is enhanced by environmental carcin
ogens, and the cellular proliferation rate, which is enhanced by agent
s that include sex hormones, inducers of chronic inflammation, and irr
itant chemicals which stimulate reactive hyperproliferation. A preferr
ed chemoprevention strategy should consist of the development of drugs
and drug combinations which will block mutagenic carcinogens or preve
nt epithelial hyperproliferation or its causes. Two examples of the in
duction of regression of intraepithelial neoplasia by chemopreventive
drugs are the regression of oral leukoplakia produced by beta-carotene
and the regression of colorectal polyps in patients with familial pol
yposis produced by sulindac. It is evident that there is a strong need
for more research on the induction of regression of intraepithelial n
eoplasia with chemopreventive agents. There is also a critical need to
identify and develop biomarkers that correlate with the appearance an
d regression of intraepithelial neoplasia.