Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

Abstract

Field cancerization denotes the occurrence of aberrant cells in tumor adjacent histologically normal tissues (TAHN). To characterize field cancerization in prostate cancer, we used RNA from paired patient tumor and TAHN tissues excised at 1 cm from the tumor margin and subjected them to microarray expression analysis comparative to RNA from normal cancer-free prostatic tissues. Eleven novel transcripts were significantly up-regulated in TAHN tissues and also in tumors. Expression of early growth response protein 1, tristetraprolin, testican, and fatty acid synthase, mutually up-regulated at different levels in tumors and TAHN tissues was confirmed by quantitative reverse transcriptase PCR in the experimental and in an independent validation set. This study offers proof of expressional changes in field cancerized prostatic TAHN tissues at defined distances from tumor margins. Markers of field cancerized prostatic tissues could be early diagnostic indicators in biopsies after abnormal prostate-specific antigen and digital rectal examination and independent of cancerous histology and/or early targets for chemo-preventive intervention in pre-malignant disease.