CARCINOMA PROSTATE
AYISHA SUHAIL
ROLL NO:18
DEFINITION
Malignant tumour arising from the glandular epithelium of prostate
gland.
Adenocarcinoma is the most common malignant tumour of man.
ETIOLOGY; RISK FACTORS
Age
Androgens
Hereditary factors
Environmental factors
Acquired somatic mutations
AGE
More common in >50 years old (disease of aging)
ANDROGENS
Androgens bind to androgen receptor and express progrowth and
prosurvival genes and leads to proliferation of cells.
By acquired receptor gene amplification (increased sensitivity to low
androgen level) and the mutations which permit ligand
independent receptor activation , most prostatic carcinomas are
resistant to androgen blockade.
Heredity
Men with first degree relatives affected with prostate carcinoma
have a 2 fold increased risk.
Germ line variants which increasing the risk
Activation of MYC oncogene.
Inactivation of DNA repair gene.
ENVIRONMENTAL FACTORS
Exposure to carcinogens , estrogens , oxidants can damage the prostatic
epithelium. These damaged epithelial cells may aquire genetic and epigenetic
changes which lead to the development of cancer.
Dietary carcinogens: charred red meat and animal fat
Infections : sexually transmitted infections like trichomoniasis ,gonorrhoea cause
chronic inflammation of [Link] is link between environmental carcinogens
and cancer.
Mutations
TPRSS2-ETS fusion gene
Amplification of MYC and deletion of PTEN
Loss of TP53 (by deletion or mutation) and deletionof RB,
amplifications of the androgen receptor gene.
Epigenetic events: Epigenetic silencing of the GSTPI (glutathione-S-
transferase)gene . Its product GSTP1 is antioxidant helping in
detoxification.
PATHOGENESIS
PRECURSOR LESIONS characterized by prostatic intraepithelial neoplasia(PIN)
It’s the preinvasive stage of the neoplasia.
The high grade PIN(HGPIN) is the earliest recognizable change.
There will be proliferation of atypical cells in the pre-existing prostatic ducts and
acini.
Nuclear enlargement with prominent nucleoli.
Basal layer is partly lost.
MORPHOLOGY
GROSS
Location; peripheral zone
Cut section; gritty and firm.
MICROSCOPY
3 criteria for diagnosis; Architecture
Absence of basal cells
Nuclear atypia
ARCHICTURE
• Neoplastic glands are smaller than benign glands , more crowded ,lack branching and
papillary infoldings
• Glands lined by single uniform layer of cuboidal or columnar epithelium and no basal
layer.
TUMOUR CELLS
• Enlarged nucleus with prominent one or more nucleoli.
• Cytoplasm;pale clear to dark purple
INTRALUMINAL CONTENTS
• Prostatic crystalloids in the lumen are dense eosinophilic crystal like structures
• Mitottic figures are more common in high grade cancers.
SPREAD
Local spread : invasion of prostatic capsule
: periprostatic tissue(fat),seminal vesicle,periurethral zone
Lymphatic spread : via thoracic duct to the lung
: via prostatic venous plexus to inferior venacava
Hematogenous spread : Bones of the axial skeleton( osteoblastic )
: visceral organs ( lung,liver,adrenal glands )
CLINICAL COURCE
Early asymptomatic stage: discovered by rectal examinanation or
elevated PSA(prosate specific antigen)
Advanced : urinary symptoms like dysuria,frequency,hematurea.
Bone metastasis leads to back pain.
Tumour markers
Prostate specific antigen(PSA)
organ specific , not cancer specific
useful in assessing response to therapy and detecting recurrence.
Grading and staging ( GLEASON SYSTEM )
based on glandular patterns
Grade 1 & 2 : most well differentiated consists of uniform and round
neoplastic glands that form well circumscribed nodules.
Grade 3 : single,separate,well formed glands , glands with pinpoint
lumina , medium sized or large glands
Grade 4 : coalescent or fused glands with>1 lumen and absence of
intervening stroma
Grade 5 : do not form glands and infiltrate stroma in cords,sheets
and solid nests. It shows comedo necrosis.
score/sum: adding grades of most commen and high grade pattern
on given core.
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