Prostate

PROSTATE

The prostate is a gland in the male

reproductive system that produces fluid for
semen and helps expel semen during
ejaculation:
Location
The prostate is located below the bladder and
above the pelvic floor muscles, and surrounds
the urethra.

Figure 21.27 Normal prostate gland, with basal

cell and secretory cell layers.
In a normal adult, the
prostate weighs
approximately 20 g and can
be divided into four
biologically and anatomically
distinct regions, the
peripheral, central, transition,
and periurethral zones
 Inflammatio
n
● Prostatitis is inflammation
or swelling of the prostate
gland. When symptoms
start gradually and linger
for more than a couple of
weeks, the condition is
called chronic prostatitis.
 Inflammatio
n
● Acute bacterial prostatitis
- Cause: bacteria that reach the prostate through contaminated urine or
through the bloodstream. It can also occur after medical procedures
involving the urethra or prostate.
- most cases are caused by various strains of E. coli, other gram-
negative rods, enterococci, and staphylococci.
- Symptoms: Fever, chills, pain, difficulty urinating, and a tender prostate.
- Treatment: Antibiotics.

E. coli
staphylococci
enterococci
Inflammatio
n
● Chronic bacterial prostatitis
- Cause: Patients often have a history of recurrent urinary tract
infections (cystitis, urethritis) caused by the same organism

- Symptoms: low back pain, dysuria, and perineal and

suprapubic discomfort, though it also may be asymptomatic.
Unlike acute bacterial prostatitis, chronic bacterial prostatitis
doesn’t usually cause fever and chills.

- Treatment: Long-term antibiotics.

Inflammatio
nChronic non-bacterial prostatitis
- the most common form of prostatitis, is often referred to clinically
as chronic pelvic pain syndrome.

- Cause: Unknown, but often associated with pelvic floor muscle

tension.

- Symptoms: Pelvic pain, urinary frequency, urgency, and pain during

ejaculation .

- Treatment: Pain management, physical therapy, and medications.

 Inflammatio
n
Granulomatous prostatitis

● Cause: - Immune response to a foreign substance, such as

bacteria, fungi, or certain medications.
- It is indistinguishable from chronic bacterial prostatitis in
terms of signs and symptoms, but there is no history of
recurrent urinary tract infection.
● Symptoms: Similar to chronic prostatitis.
● Treatment: Depends on the underlying cause, often
involving corticosteroids or immunosuppressants.
Benign Enlargement
Benign Prostatic Hyperplasia - BPH (also
referred to as nodular hyperplasia))
- is the most common benign prostatic
disease in men older than age 50 years
- It is not a premalignant lesion.

★ Etiology and Pathogenesis

→ prostate cells proliferate, increasing the

volume and weight of the gland.

The exact cause of benign prostatic hyperplasia is unknown. Some experts

have suggested that the condition may be caused by changes in hormone
balance in older men (As men get older, the balance of hormones, particularly
testosterone and dihydrotestosterone (DHT), can change, leading to prostate
growth.
 MORPHOLOGY
In BPH, the weight of the enlarged prostate
often increases three- to fivefold (60 to 100 g),.
BPH affects the transition zone and thus may
encroach on the urethra, compressing it to a
slit-like orifice
On cross-section, hyperplastic nodules are
seen that vary in color and consistency
depending on their cellular content
The glands are lined by two layers of cells, an
inner columnar secretory cell layer and an
outer layer of cuboidal or flattened basal
epithelium (Fig. 21.29C), and infolding of the
glands may produce a papillary architecture.
Clinical features
● The main symptoms of BPH are due to urinary obstruction
caused by prostatic enlargement and stromal smooth muscle–
mediated contraction.

● The increased resistance to urinary outflow leads to bladder

hypertrophy and distention, accompanied by urine retention.

● This obstruction leads to various symptoms such as frequent

urination, difficulty starting and stopping urine flow, weak urine
stream, and nighttime urination. In severe cases, acute urinary
retention may occur, requiring immediate catheterization.
 Neoplas
ms
Adenocarcinoma
- In the United States, adenocarcinoma of the prostate is
the most common form of cancer in men, with an expected
174,650 new cases in 2019, accounting for 20% of all male
cancers.
- Prostate cancer is the second cause of cancer-related death
in men, surpassed only by lung cancer
- It is largely a disease of aging (70% in men between the ages
of 70 and 80 years.)
Epidemiology and Pathogenesis.
★ Environmental Factors
Exposure to carcinogens, estrogens, and oxidants →
damage prostatic epithelium → setting the stage for
acquisition of genetic and epigenetic changes → lead to
cancer development
- The "Western diet," rich in
charred red meat and animal
fats, is a particular concern.
These dietary components
can lead to the formation of
carcinogens, which can
damage prostatic epithelium
and contribute to cancer
development.
 ★ Inherited Genetic Factors
Genetic factors play a significant role in prostate cancer development.
Family history is a strong risk factor, with first-degree relatives of
affected individuals having a doubled risk.
Specific genetic variants have been identified that contribute to prostate
cancer risk. These include:
● Common Variants with Modest Risk: EX: MYC is an important
oncogene involved in cell growth and proliferation. When MYC is
overexpressed, it can contribute to cancer development.
● Rare Variants with High Risk: Mutations in DNA repair genes like
BRCA2 and mismatch repair genes (associated with Lynch syndrome).
● Developmental gene variants: Variants in the HOXB13 gene, which
plays a role in prostate development. Variations in HOXB13 can
increase the risk of prostate cancer by disrupting normal prostate
development.
★ Androgens
Androgen Dependence:
- Prostate cancer cells, like normal prostate cells, rely on androgens to grow and survive.
When androgen levels are reduced through castration (surgical removal of the testes)
or anti-androgen therapy (blocking the action of androgens), the cancer cells often
shrink or stop growing.
Androgen Independence and Resistance:
Tumors escape through a variety of mechanisms, including acquisition of
hypersensitivity to low levels of androgen: ligand-independent AR activation
(e.g., via splice variants that lack the ligand binding domain); mutations in AR
that allow it to be activated by non-androgen ligands; and other mutations or
epigenetic changes that activate alternative signaling pathways and bypass the
need for AR altogether
These mechanisms allow prostate cancer cells to continue growing and
proliferating, even in the absence of significant levels of circulating androgens
★ Acquired Genetic and Epigenetic Alterations.
The most common genetic alteration in the prostate is a chromosomal
rearrangement that juxtaposes the coding sequence of an ETS family
transcription factor gene (most commonly ERG or ETV1) next to the
androgen-regulated TMPRSS2 promoter.

Loss of Tumor Suppressor Genes:

● p27: This gene encodes a protein that inhibits cell cycle progression. Loss of p27 can
lead to uncontrolled cell growth.
● PTEN: This gene encodes a protein that inhibits cell growth and survival. Loss of PTEN
can promote tumor growth and resistance to therapy.
● TP53: This gene encodes a tumor suppressor protein that helps repair DNA damage.
Loss of TP53 can lead to genomic instability and increased cancer risk.
● RB: This gene encodes a protein that regulates cell cycle progression. Loss of RB can
lead to uncontrolled cell growth.
 ★ Precursor lesions
PIN (prostatic intraepithelial neoplasia ) is considered a precursor lesion to
prostate cancer. It's a condition where the cells lining the prostate glands show
abnormal growth. While PIN itself doesn't always progress to cancer, it's often
found in men who later develop prostate cancer.
The Link Between PIN and Prostate Cancer:
● Shared Location: Both PIN and prostate cancer are more commonly found in
the peripheral zone of the prostate.
● Increased Frequency: Prostates with cancer often have a higher prevalence
of PIN.
● Molecular Overlap: Many of the molecular changes seen in PIN are also
found in prostate cancer, suggesting a direct link.
Grading and Staging.
- Grade and stage are the most important prognostic
factors in prostate cancer
- The grade describes the appearance of cancer cells, while the stage
describes how far the cancer has spread.
Gleason system, which stratifies prostate cancer into five grades on
the basis of glandular patterns of growth

● Grade 1. The cells look very much like normal prostate cells.
● Grades 2-4. Cells that score lower look closest to normal and represent a
less aggressive cancer. Those that score higher look the furthest from
normal and will probably grow faster.
Clinical Features
- Localized prostate cancer is asymptomatic (no symptoms) and
is usually discovered by the detection of a suspicious nodule on
rectal examination or elevated serum prostate-specific antigen
(PSA) level.

- Patients with clinically advanced prostatic cancer may present

with symptoms of urinary obstruction.

- Measurement of serum PSA levels is widely used to assist with

the diagnosis and management of prostate cancer but is
controversial
Miscellaneous Tumors

● Prostate adenocarcinomas may also arise from prostatic

glands and ducts.
● Ductal adenocarcinomas, particularly those originating from
periurethral ducts, may present similarly to bladder cancer,
causing hematuria and urinary obstruction⇒ These types
often have a poorer prognosis.
● Prostate cancers may show squamous differentiation, either
following hormone therapy or de novo, resulting in either
adenosquamous or pure squamous cancer
● Prostate cancers that reveal abundant mucinous secretions in
greater than 25% of the tumor are termed colloid carcinoma
of the prostate.
Miscellaneous Tumors

● The most aggressive variant of prostate cancer is

small-cell carcinoma
● The most common tumor to secondarily involve the
prostate is urothelial cancer
1. What form is the most common in prostatitis?
2. How does a loss of TP53 function contribute to
prostate cancer development?