High-grade prostatic intraepithelial neoplasia as an exposure biomarker for prostate cancer chemoprevention research.

There is a tremendous need for exposure biomarkers, which need to function as intermediate end-points in cancer chemoprevention studies. Likely candidates include process biomarkers, atypical adenomatous hyperplasia, and a newly identified atrophic state. High-grade prostatic intraepithelial neoplasia (HGPIN) has the potential to be a useful exposure biomarker, having substantial predictive value for prostate cancer in chemoprevention trials. A limitation of the use of HGPIN as a biomarker is accessibility, since it requires the use of a highly invasive procedure that would not normally be applied unless malignancy is suspected to be present. However, most other biomarkers of prostatic tissue are similarly invasive. The HGPIN lesion appears to be highly measurable; however, problems of sampling coupled with the heterogeneity of the prostate raise questions about the degree to which the presence of HGPIN can be seen to characterize a given person's prostate gland. HGPIN has the advantage that it appears to be quite highly proximal to the development of cancer and to be modifiable. It remains less clear to what degree it reflects the exposures that are believed to alter prostate cancer risk. HGPIN has been identified as a clinical entity only recently and much additional research on the utility of this marker is needed.