Evidence for field cancerization of the prostate

Abstract

Background: Field cancerization, which is not yet well-characterized in the prostate, occurs when large areas of an organ or tissue surface are affected by a carcinogenic insult, resulting in the development of multi-focal independent premalignant foci and molecular lesions that precede histological change.

Methods: Herein, we review the cumulative body of evidence concerning field effects in the prostate and critically evaluate the methods available for the identification and validation of field effect biomarkers. Validated biomarkers for field effects have an important role to play as surrogate endpoint biomarkers in Phase II prevention trials and as clinical predictors of cancer in men with negative biopsies.

Results: Thus far, field effects have been identified involving nuclear morphometric changes, gene expression, protein expression, gene promoter methylation, DNA damage and angiogenesis. In addition to comparing cancer-adjacent benign tissue to more distant areas or to "supernormal" tissue from cancer-free organs, investigators can use a nested case-control design for negative biopsies that offers a number of unique advantages.

Conclusions: True carcinogenic field effects should be distinguished from secondary responses of the microenvironment to a developing tumor, although the latter may still lead to useful clinical prediction tools. Prostate 69: 1470-1479, 2009. (c) 2009 Wiley-Liss, Inc.

Fig. 1

Nested case–control study design for epidemiological validation of field effect tissue biomarkers.