Carcioma of Prostate

30/02
 Introduction
• Adenocarcinoma of the prostate is the most
common form of cancer in men.
• Disease of men older than age 50 years.
 Etiology and Pathogenesis
• Age: Older than 50 years.
• Race: Blacks and Caucasians. Lesser incidence in Asians.
• Family history:
 Compared with men with no family history, men with one first-
degree relative with prostate cancer have twice the risk and those
with two first-degree relatives have five times the risk of developing
prostate cancer.
 Men with a strong family history of prostate cancer also tend
to develop the disease at an earlier age.
 Men with germline mutations of the tumor suppressor BRCA2
have a 20-fold increased risk of prostate cancer, and a germline
mutation in HOXB13, a homeobox gene encoding a transcription
factor that regulates prostatic development, also confers
substantially increased risk in the small percentage of families that
carry it.
• Hormone Level:
 Androgens play an important role in prostate cancer.
 Like their normal counterparts, the growth and survival
of prostate cancer cells depends on androgens, which
bind to the androgen receptor (AR) and induce the
expression of pro-growth and pro-survival genes.
 The importance of androgens in maintaining the
growth and survival of prostate cancer cells can be
seen in the therapeutic effect of castration or
treatment with antiandrogens, which usually induce
disease regression.
• Environmental influences:
• The increased incidence of this disease upon
migration from a low-incidence region to one
with a high incidence is consistent with a role
for environmental influences. Eg: Common in
blacks and Japanese immigrants to the US.
• Diet:
• Increased consumption of fats or carcinogens
present in charred red meats has been
implicated.
• Other dietary products suspected of
preventing or delaying prostate cancer
developmentinclude lycopenes (found in
tomatoes), soy products, and vitamin D.
 Morphology
• Gross:
 When the terms “prostate cancer” or “prostate adenocarcinoma” are used without qualifications
it refers to the common or acinar variant of prostate cancer.
 Carcinoma of the prostate arises in the peripheral zone of the gland, classically in a posterior
location, where it may be palpable on rectal examination .
 Characteristically, on cross-section of the prostate the neoplastic tissue is
 gritty and firm, but when embedded within the prostatic substance it may be extremely difficult
to visualize and be more readily apparent on palpation.
 Local extension most commonly involves periprostatic tissue, seminal vesicles, and the base of the
urinary bladder, which in advanced disease may produce ureteral obstruction.
 Metastases spread via lymphatics to the obturator nodes and eventually to the para-aortic nodes.
 Hematogenous spread occurs chiefly to the bones, particularly the axial skeleton, but some lesions
spread widely to viscera.
 The bony metastases are typically osteoblastic, a feature that in men points strongly to a prostatic
origin.
 The bones commonly involved, in descending order of frequency, are lumbar spine, proximal femur,
pelvis, thoracic spine, and ribs.
• Histologically, most lesions are adenocarcinomas that produce well-
defined, readily demonstrable gland patterns.
• The glands are typically smaller than benign glands and are lined by
a single uniform layer of cuboidal or low columnar epithelium.
• In contrast to benign glands, prostate cancer glands are more
crowded, and characteristically lack branching and papillary
infolding.
• The outer basal cell layer typical of benign glands is absent.
• The cytoplasm of the tumor cells ranges from pale-clear to a
distinctive amphophilic appearance.
• Nuclei are large and often contain one or more large nucleoli. There
is some variation in nuclear size and shape, but in general
pleomorphism is not marked.
• Mitotic figures are uncommon.
• Few histologic findings on biopsy are specific
for prostate cancer, such as perineural
invasion, but in general the diagnosis is made
based on a constellation of architectural,
cytologic, and ancillary findings
Gleason Scoring System for grading Ca
Prostate
• Prostate cancer is graded using the Gleason
system, which stratifies prostate cancer into
five grades on the basis of glandular patterns
of differentiation.
• Most tumors contain more than one pattern; in such
instances, a primary grade is assigned to the dominant
pattern and a secondary grade to the second most
frequent pattern.
• The two numeric grades are then added to obtain a
combined Gleason grade or score.
• Thus, for example, a tumor with a dominant grade 3
and a secondary grade 4 has a Gleason score of 7.
• Tumors with only one pattern are treated as if their
primary and secondary grades are the same, and
hence, the number is doubled.
• Localized prostate cancer is asymptomatic, and is usually discovered by
the detection of a suspicious nodule on rectal examination or elevated
serum PSA level.
• Most prostatic cancers arise peripherally away from the urethra, and
therefore urinary symptoms occur late.
• Patients with clinically advanced prostatic cancer may present with urinary
symptoms, such as difficulty in starting or stopping the stream, dysuria,
frequency, or hematuria.
• Back pain caused by vertebral metastases.
• The finding of osteoblastic metastases by skeletal surveys or the much
more sensitive radionuclide bone scanning is virtually diagnostic of this
form of cancer in men.
• These cancers pursue a universally fatal course.
• Digital rectal examination may detect some early prostatic carcinomas
because of their posterior location, but the test suffers from both low
sensitivity and specificity.
• Serum PSA measurement is a useful but
imperfect cancer screening test, with
significant rates of false-negative and false-
positive results.
• Evaluation of PSA concentrations after
treatment has great value in monitoring
progressive or recurrent disease.