Use of Archival Tissues to Evaluate Proliferative and Apoptotic indices in Human Prostate Carcinoma and Benign Prostatic Hyperplasia.
J.O. Johnston, R.D. Snyder, H.W. Carter, J.L. Pullman and J.H. Carter, Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41074-4701.
Abstract
The prostate is unique in its potential to develop neoplasms in comparison
to the androgen-dependent sex accessory glands which rarely develop tumors.
Molecular events related to tumor induction and expression of associated
biomarkers are presumably specifically regulated in the prostate, since
all of these tissues could be exposed to similar carcinogenic potentials.
Recent evidence suggests that the neoplastic process is accompanied by changes
both in the fraction of tumor cells proliferating and those cells dying
via genetically programmed apoptosis. Increased proliferation in tumors,
if not balanced by equivalent cell death rates will result in net tumor
growth. However, in established neoplasms the amount of apoptosis is usually
seen to increase with histological grade. Prostate tumors with a high apoptotic
index, (AI), i.e., a high percentage of cells undergoing apoptotic cell
death, have previously been associated with poor prognosis. This may reflect
a relationship between the underlying level of genetic instability and tumor
progression. We have examined the epithelial component of 25 human prostate
carcinomas of similar Gleason grades for both apoptosis, as measured by
in-situ end-labeling of DNA double strand breaks by terminal deoxynucleotidyl
transferase (TUNEL) assay, and proliferative index (PI), as measured via
immunohistochemical techniques using MIB-1 antibody against Ki-67. These
paraffin-imbedded prostate carcinoma tissues which were obtained at surgery
exhibited a wide range of AI and PI values. We have also found a similar
range of AI and PI values in "normal" glandular epithelial cells
in a study of prostatic tissues from 80 men with benign prostatic hyperplasia.
AI values of prostatic tissues from men without prostate cancer may reflect
inherently high or low levels of genetic instability. Determination of age-adjusted
AI and PI values for noncancerous prostate tissues may establish critical
biomarker levels that will help identify men at increased risk of developing
prostate cancer.