Eble JN, Sauter G., Epstein JI, Sesterhenn IA - iarc

expression of PSMA in serum of both normal
individuals and prostate cancer
patients using western blots have provided
conflicting results in some laboratories
{635,1838,1841,2214}.
Reverse transcriptase-polymerase chain
reaction
RT-PCR is an extremely sensitive assay,
capable of detecting one prostate cell
diluted in 10 8 non-prostate cells. This high
degree of sensitivity mandates that
extreme precaution be taken to avoid both
cross-sample and environmental contamination.
Because of the high sensitivity of
RT-PCR, there is the possibility that
extremely low-level basal transcriptions of
prostate-specific genes from non-prostate
cells will result in a positive RT-PCR signal.
More recently, basal PSA mRNA levels
were detected in a quantitative RT-PCR in
individuals without prostate cancer, thus
suggesting the need to quantitate the RT-
PCR assay in order to control for basal
transcription {2730}. These problems with
RT-PCR have limited its clinical utility
{1780,1927}.
Methods of tissue diagnosis
Needle biopsies
The current standard method for detection
of prostate cancer is by transrectal ultrasound-guided
core biopsies. Directed
biopsies to either lesions detected on digital
rectal examination or on ultrasound
should be combined with systematic biopsies
taken according to a standardized
protocol {1008,1703}. The sextant protocol
samples the apex, mid and base region
bilaterally {1099}. Sextant biopsies aim at
the centre of each half of the prostate equidistant
from the midline and the lateral
edge while the most common location of
prostate cancer is in the dorsolateral
region of the prostate.
Several modifications of the sextant protocol
have been proposed. Recent studies
have shown that protocols with 10 to
13 systematic biopsies have a cancer
detection rate up to 35% superior to the
traditional sextant protocol {105,724,
2151}. This increased yield relates to the
addition of biopsies sampling the more
lateral part of the peripheral zone, where
a significant number of cancers are
located.
Approximately 15-22% of prostate cancers
arise in the transition zone, while
sextant biopsies mainly sample the
peripheral zone. Most studies have
found few additional cancers by adding
transition zone biopsies to the sextant
protocol (1.8-4.3% of all cancers detected)
and transition zone biopsies are usually
not taken in the initial biopsy session
{778,2598}.
Handling of needle biopsies. Prostate
biopsies from different regions of the gland
should be identified separately. If two
cores are taken from the same region, they
can be placed into the same block.
However, blocking more than two biopsy
specimens together increases the loss of
tissue at sectioning {1272}. When atypia
suspicious for cancer is found, a repeat
biopsy should concentrate on the initial
atypical site in addition to sampling the
rest of the prostate. This cannot be performed
unless biopsies have been specifically
designated as to their location. The
normal histology of the prostate and its
adjacent structures differs between base
and apex and knowledge about biopsy
location is helpful for the pathologist. The
location and extent of cancer may be critical
for the clinician when selecting treatment
option {2151}. The most common fixative
used for needle biopsies is formalin,
although alternative fixatives, which
enhance nuclear details are also in use. A
potential problem with these alternative fixatives
is that lesions such as high-grade
prostatic intraepithelial neoplasia may be
over-diagnosed.
Immunohistochemistry for high molecular
weight cytokeratins provides considerable
help in decreasing the number of
inconclusive cases from 6-2% {1923}. It
has therefore been suggested that intervening
unstained sections suitable for
immunohistochemistry are retained in
case immunohistochemistry would be
necessary. Intervening slides are critical
to establish a conclusive diagnosis in
2.8% of prostate biopsies, hence, sparing
a repeat biopsy {939}.
Transurethral resection of the prostate
When transurethral resection of the
prostate (TURP) is done without clinical
suspicion of cancer, prostate cancer is
incidentally detected in approximately 8-
10% of the specimens. Cancers detected
at TURP are often transition zone
tumours, but they may also be of peripheral
zone origin, particularly when they
are large {941,1685,1686}. It is recommended
that the extent of tumour is
reported as percentage of the total specimen
area. If the tumour occupies less
Fig. 3.09 Needle biopsies sampling the lateral part
of the peripheral zone (PZ) improve detection of
prostate cancer (red).
than 5% of the specimen it is stage T1a,
and otherwise stage T1b. However, in the
uncommon situation of less than 5% of
cancer with Gleason score 7 or higher,
patients are treated as if they had stage
T1b disease. Most men who undergo
total prostatectomy for T1a cancer have
no or minimal residual disease, but in a
minority there is substantial tumour located
in the periphery of the prostate {711}.
Handling of TUR specimens. A TURP
specimen may contain more than a hundred
grams of tissue and it is often necessary
to select a limited amount of tissue
for histological examination.
Submission should be random to ensure
that the percentage of the specimen area
involved with cancer is representative for
the entire specimen. Several strategies
for selection have been evaluated.
Submission of 8 cassettes will identify
almost all stage T1b cancers and
approximately 90% of stage T1a tumours
{1847,2223}. In young men, submission
of the entire specimen may be considered
to ensure detection of all T1a
tumours. Guidelines have been developed
for whether additional sampling is
needed following the initial detection of
cancer in a TURP specimen {1673}.
Fine needle aspiration cytology
Before the era of transrectal core biopsies,
prostate cancer was traditionally
diagnosed by fine needle aspiration
(FNA). FNA is still used in some countries
and has some advantages. The technique
is cheap, quick, usually relatively
painless and has low risk of complications.
In early studies comparing FNA
and limited core biopsy protocols, the
sensitivity of FNA was usually found to be
comparable with that of core biopsies
{2765}. However, the use of FNA for diagnosing
prostate cancer has disadvan-
168 Tumours of the prostate