Molecular cancer phenotype in normal prostate tissue.
BACKGROUND
Insufficient sensitivity and specificity of prostate biopsies for cancer detection.


OBJECTIVE
Based on evidence from our microarray analyses, we hypothesized that considerable molecular changes precede morphologically detectable malignant transformation of prostate epithelial tissues. The identification of such changes could lead to novel strategies in the clinical management of prostate cancer.


METHODS
Histologically normal, fresh prostate tissue from prostate cancer patients, healthy donors, and cancer suspect patients with continuous negative biopsies were analyzed.


METHODS
To identify molecular changes between 29 tumor-free prostate tissues from healthy donors and 27 patients with proven prostate cancer, we performed a global microarray screening. Based on this screening as well as literature data, we selected a subset of 29 genes for validation by arrayed real-time reverse transcription-polymerase chain reaction (RT-PCR) using histologically tumor-free biopsy samples from 114 patients representing three prostate cancer risk groups.


CONCLUSIONS
We identified five genes (FOS, EGR1, MYC, TFRC, and FOLH1), which displayed significant differential expression between morphologically normal prostate tissues from men of each of the three risk groups. These results were independent from age, prostate-specific antigen (PSA), frequency and timing of previous prostate biopsies, tissue composition, tumor stage, and tumor grade. In univariate logistic regression analyses, the transcript levels of these genes were found to be highly indicative for the presence or absence of cancer in the entire prostate. The study was designed as a proof of principle. The clinical relevance of our results has to be evaluated in a larger clinical setting.


CONCLUSIONS
Our results suggest a measurable molecular cancer phenotype in histologically normal prostate tissue indicating the presence of prostate cancer elsewhere in the organ.
Schlomm
Thorsten
T
Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Germany. tschlomm@uke.uni-hamburg.de
Hellwinkel
Olaf J C
OJ
Buness
Andreas
A
Ruschhaupt
Markus
M
Lübke
Andreas M
AM
Chun
Felix K
FK
Simon
Ronald
R
Budäus
Lars
L
Erbersdobler
Andreas
A
Graefen
Markus
M
Huland
Hartwig
H
Poustka
Annemarie
A
Sültmann
Holger
H
D015870:Gene Expression; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D010641:Phenotype; D011467:Prostate / Q000033:anatomy & histology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology