Türkeri_EU_Genito.qxp 21/2/08 3:03 pm Page 13
Prostate Cancer
New Markers for Prostate Cancer
a report by
Levent H Türkeri
Professor of Urology, Marmara University School of Medicine
Prostate cancer is a major health problem as it is one of the most protein product. Its expression was shown to be androgen-dependent
common malignancies and a major cause of cancer mortality. and increased rapidly in a dose-dependent manner.
8
Diagnosis is made by prostate biopsy, although decision-making is not
always straightforward. Screening and early diagnosis are largely Using a quantitative gene expression analysis, PCA3 was shown to be
based on prostate-specific antigen (PSA) testing and digital rectal regulated by a unique prostate-cancer-specific transcriptional
examination. Introduction of PSA into clinical practice in the 1980s mechanism and may provide a sensitive and specific tool to detect
allowed early detection and created a major stage shift.
1,2
prostate cancer.
9
PCA3 expression was mostly undetectable in other
tissues, including bladder and testis. PCA3 mRNA expression levels
However, further studies indicated that PSA is not an ideal biomarker were low in normal prostate and absent in all other tissues except the
for prostate cancer detection. Results from a clinical trial reported that kidneys, in which the level of expression was insignificant.
there is no absolute lower value of PSA below which there is a
negligible risk of prostate cancer.
3
Also, PSA has limited specificity In addition, PCA3 mRNA expression could not be detected in 39
since it is expressed in a normal prostate as well. Abnormal PSA values, tumour samples other than prostate cancer, representing nine
specifically those in the 4–10ng/ml range, can occur in men with malignancies.
9
Median upregulation of PCA3 expression from normal
to tumour tissue was 34-fold in this study (p<0.00019). The area under
the curve (AUC) of receiver operating characteristic (ROC) analysis,
Significant efforts have been initiated
which represents the diagnostic efficacy of the test, was 0.98,
indicating an impressive discriminative power. However, there was no
in the discovery of new biomarkers
significant correlation between PCA3 expression and tumour stage or
for prostate cancer in different Gleason score.
bio-specimens, including serum,
In an effort to enhance the prognostic efficacy of PCA3 testing, various
urine and prostatic tissue.
groups have assessed the the expression of urinary PCA3 in comparison
with PSA mRNA (PCA3 score: ratio of PCA3 mRNA to PSA mRNA
multiplied by 10
3
). In a study by Groskopf et al., the median PCA3 ratios
benign prostate conditions such as benign prostate hyperplasia and for the healthy, biopsy-negative and biopsy-positive groups were 4.5, 27
prostatitis. Indeed, only 25% of individuals who undergo biopsies are and 81.8, respectively (p<0.01).
10
ROC-curve analysis of pre-biopsy PCA3
actually positive for prostate cancer.
1
Therefore, PSA is not a score as a diagnostic indicator revealed an AUC of 0.746 in comparison
dichotomous (yes–no) marker, but rather reflects a continuum of risk with 0.575 when absolute copy numbers of PCA3 mRNA were used
of disease presence.
3
instead of the ratio value. At a fixed cut-off value of 50x10
-3
, the sensitivity
of PCA3 score in diagnosis of prostate cancer was 69%, with a specificity
Thus, more specific prostate cancer biomarkers need to be identified
to aid the traditional diagnosis of cancer by a pathologist who relies
on architectural alterations in the cells and/or tissues.
4
Significant
Levent H Türkeri is a Professor of Urology in the Department
of Urology at Marmara University School of Medicine,
efforts have been initiated in the discovery of new biomarkers for
Istanbul. He is also Director of the Ergun Özalp Basic
prostate cancer in different bio-specimens, including serum, urine
Research Laboratory at the same university. He is a Board
and prostatic tissue.
Member of the European Society of Oncological Urology
(ESOU) and a member of the Société Internationale
d'Urologie (SIU), the American Association of Urology
A Genetic Marker of Prostate Cancer
(AUA), the European Association of Urology (EAU), the
Society for Basic Urological Research (SBUR) and the
Among the newer molecular biomarkers for prostate cancer diagnosis
European School of Urology (ESU). He has received numerous awards, including the Health
is the product of the prostate cancer gene (PCA3), which is a prostate- Sciences Award from the Eczacbai Scientific Research and Award Foundation in 1995, the
specific non-coding messenger RNA (mRNA).
5,6
PCA3 is encoded on
Prize of the President from the XIII Congress of the EAU for outstanding contribution to
urological oncology in 1994 and the Outstanding Academic Award from Marmara
chromosome 9 and highly overexpressed in more than 95% of prostate
University in 1994. Professor Türkeri earned his certification in basic microsurgery and
cancers,
5,6
and the rate of upregulation was found to be between six-
undertook a residency in urology at the Marmara University School of Medicine in 1989
and 1991, respectively.
and 1,500-fold (median 66-fold) in prostate cancers compared with
adjacent non-neoplastic tissue.
6,7
The function of PCA3 is not known at
E: turkeri@marmara.edu.tr
the moment. It is a short sequence of non-coding DNA without any
© TOUCH BRIEFINGS 2007 13