CARCINOMA OF THE PROSTATE Flashcards
the most common form of cancer in men
Adenocarcinoma of the prostate
Adenocarcinoma of the prostate is uncommon before the age
50
Pathogenesis of prostate carcinoma
androgens,
heredity,
environmental factors, and acquired somatic mutations
Androgens are of central importance because they
provide the “soil,” the cellular context
does not develop in
males who are castrated before puberty
cancers →often regress for a time in response to
surgical or chemical castration
tumors that recur in the face of anti-androgen therapies still depend on
gene products regulated by androgen receptors for their growth and survival
there is no evidence that
androgens initiate carcinogenesis, nor are androgen levels associated with prostate cancer risk
there is an increased risk among
first-degree relatives of patients
• Prostate cancer
Uncommon in
Asia
highest among
African-Americans and in Scandinavian countries
Genome-wide association studies have identified
a number of genetic variants that are associated with increased risk for developing prostate cancer. Although each variant carries only a small increased risk, the effect is multiplicative, such that men with multiple risk alleles may have up to a 5-fold increase in risk compared to the general population.
Environment
in Japanese immigrants to the United States the incidence of the disease rises as the diet in Asia becomes more westernized
Acquired genetic aberrations
as in other cancers, genetic aberrations are the actual drivers of cellular transformation
actual drivers of cellular transformation
genetic aberrations
The most common gene rearrangements in prostate cancer create fusion genes
TMPRSS2-ETS fusion genes
TMPRSS2-ETS fusion genes is found in
40% to 60% of prostate cancers
TMPRSS2-ETS fusion genes occur relatively early in
tumorigenesis
Other mutations commonly lead to activation of
the PI3K/AKT signaling pathway
Most common mutations include
are loss-of-function mutations involving the tumor suppressor PTEN
GROSS
Carcinomas detected clinically are usually not visible grossly.
• More advanced lesions appear as firm, gray-white lesions with ill-defined margins
• infiltrate the adjacent gland
LM
moderately differentiated adenocarcinomas with well-defined glands
Glands in LM
typically are smaller than benign glands
Glands are
lined by a single uniform layer of cuboidal or low columnar epithelium, lacking the basal cell layer seen in benign glands
are crowded together
characteristically lack branching and papillary infolding
the cytoplasm of the tumor cells ranges from
pale-clear (as in benign glands) to a distinctive amphophilic (dark purple) appearance
nuclei
are enlarged and often contain one or more prominent nucleoli
some variation
in nuclear size and shape is usual
… is not marked
pleomorphism
.. are uncommon
mitotic figures
With increasing grade
irregular or ragged glandular structures, cribriform glands,
sheets of cells, or
infiltrating individual cells are present
Grade 1
→ the most well differentiated tumors,
grade 5
→no glandular differentiation
Most tumors are patterns
3, 4, or 5
the majority of tumors contain
more than one pattern
primary grade is assigned to
and a secondary grade to
the dominant pattern
the next most frequent pattern.
The two numerical grades are then
added to obtain a combined Gleason score.
Tumors with only one pattern are treated
as if their primary and secondary grades are the same →the number is doubled
The most differentiated tumors have a Gleason score of
2 (1 +1)
least differentiated tumors merit a score of
10 (5 +5)
approximately 80% of cases in remaining tissue harbors→
high-grade prostatic intraepithelial neoplasia (HGPIN)
high-grade prostatic intraepithelial neoplasia (HGPIN)
80% of cases in remaining tissue harbors
Many of the molecular changes seen in invasive cancers are also seen in
HPIN
Clinical Features
small, nonpalpable, asymptomatic lesions discovered on needle biopsy performed to investigate an elevated serum prostate-specific antigen (PSA) level
Some 70% to 80% of prostate cancers arise in
the outer (peripheral) glands,
subset of outer glands prostate cancers may be palpable as
irregular hard nodules on digital rectal examination.
prostate cancer is less likely than BPH to cause ….. because..
urethral obstruction in its initial stages
of the peripheral location
Locally advanced cancers often infiltrate
the seminal vesicles and periurethral zones of the prostate may invade the adjacent soft tissues,
the wall of the urinary bladder, or less commonly the rectum
Bone metastases, particularly to… are frequent late in the disease and typically cause ..
that can be detected on ..
axial skeleton,
osteoblastic (bone-producing) lesions
radionuclide bone scans.
most widely used test in the diagnosis and management of prostate cancer
The PSA (prostate specific antigen) assay
PSA as a biomarker is that it is not cancer specific , may also increase in
BPH,
prostatitis,
prostatic infarcts,
instrumentation of the prostate, and ejaculation
Conversely, … of patients with organ confined prostate cancer have PSA values below the cutoffs
20% to 40%
The most common treatments for clinically localized prostate cancer are
radical prostatectomy and radiotherapy.
The prognosis after radical prostatectomy is based on
the pathologic stage,
whether the margins of the resected specimens are free of tumor, and Gleason grade
