world cancer report - iarc

Prostate
Bladder
Rectum
Fig. 5.47 Diagram describing patient configuration
during transrectal ultrasound imaging of the
prostate gland, which is an important technique
used to measure prostate volume and to direct
biopsies in prostatic tissue.
Fig. 5.48 A premalignant lesion of the prostate
gland: this biopsy shows prostatic intraepithelial
neoplasia (arrow) within a dilated gland.
Fig. 5.49 A biopsy from the prostate gland showing
a focus (arrow) of moderately differentiated
adenocarcinoma with tubular architecture.
Detection
The presence of lower urinary tract symptoms
(e.g. difficulty in urinating, frequent
need) above age 50 are mostly due to concomitant
benign prostatic hypertrophy.
Latent cancer can progress to adenocarcinomas,
which can infiltrate local urogenital
organs and give rise to distant metastases,
particularly to the bones. Digital
rectal examination is the simplest way to
detect anatomical abnormalities of the
210 Human cancers by organ site
Basal cells Luminal cells
NORMAL
EPITHELIUM
Secretions
Loss of 8p21
NKX3.1
PROSTATIC
INTRAEPITHELIAL
NEOPLASIA (PIN)
Loss of basal cells
Loss of 10q
PTEN
Fig. 5.50 Stages of prostate cancer progression are correlated with loss of specific chromosome regions
and of candidate tumour suppressor genes.
prostate gland, and asymmetry and
induration are indicative of prostate cancer.
Raised levels of PSA may confirm the
suspicion and mandate an ultrasoundguided
biopsy, after the patient has been
informed of the consequences of both
medical procedures [4]. Good clinical
practice requires that symptomatic
patients need a differential diagnosis
(analysis of clinical data to determine specific
nature of disease) whereas asymptomatic
patients, especially those over 70
years of age, must be counselled as to the
benefits and disadvantages of further
investigation and treatment. Imaging provides
no further support to confirm the
suspicion of prostate cancer. Transrectal
ultrasound guided biopsies establish the
dimensions of the prostate gland and
enable effective location of the usual six
core biopsies (Fig. 5.47). Radiological
examinations such as CT scans, MRI and
especially bone scans, are performed only
in order to stage a diagnosed cancer.
Radiolabelled immunoproteins may well
offer a potential imaging improvement.
Pathology and genetics
Cancer of the prostate is a slow but continuously
growing form of neoplasia that
is present in its preclinical form in men
from the age of 30, remaining latent for
up to 20 years before progressing to the
aggressive, malignant clinical cancer that
generally attains its peak incidence in
the seventh decade. Prostatic intraepithelial
neoplasia (Fig. 5.48) is thought to
represent the precursor of prostate can-
INVASIVE
CARCINOMA
Loss of basal lamina Androgen-independence
Loss of 13q
RB
Loss of 17p
p53
METASTASIS
cer. Microfocal, latent or incidental
prostate cancer are terms used to
describe small histological tumours
found at autopsy, or in surgical specimens,
the prevalence of which is correlated
with age. The studies of Sakr [5]
directed attention to the relatively high
incidence of these microscopic cancers
before the age of 50.
Most instances of prostate cancer are
adenocarcinomas (Fig. 5.49), generally
heterogeneous, that develop primarily in
the peripheral zone of the prostate gland.
A clinical cancer is recognized as having
a volume over 0.5 cm 3 and is less well
differentiated than the latent cancers.
Slow growth with long doubling times, as
well as de-differentiation over time, even
in the advanced stages of the disease,
are the hallmarks of prostate cancer [3].
The stages of progression are associated
with specific genetic alterations.
It is estimated that up to 10% of all cases
of prostate cancer may be inherited. Two
familial genetic susceptibility loci have
thus far been mapped to the X chromosome
and to chromosome 1p [6].
Prostate cancer is genetically unstable
and its genomic mutations can be divided
into five major types: subtle sequence
changes, alterations in chromosome
number (aneuploidy), chromosome translocations,
gene amplifications and allelic
deletions. Tumour growth suppressor
proteins such as p53 and bcl-2 are currently
being evaluated as prognostic factors,
together with an associated wide
array of other genetic alterations [7-9].