Reproductive System Part I (Prostate)

Question 1

__________

-an organ forming part of the male reproductive system

-location
—–under the bladder,
—–behind the pubic bone
—–in front of the bowel and rectum

-doughnut shape, wraps around the urethra

-surrounded by the nerves that cause erections

-about size and shape of walnut in younger men

Answer 1

Prostate

Question 2

Structure of Prostate (1 of 2)

______________ zone: largest area of the prostate
—–palpable by Digital Rectal Exam (DRE)
—–most prostate cancers occur here
—–majority of glands here

____________ zone:surrounds urethra passing prostate zone
—–enlarges with benign prostatic hyperplasia (BPH: non-cancerous enlargement of prostate)
—–beginning around age 40, transition zone begins to increase in size and eventually becomes largest zone of prostate

Answer 2

Peripheral

Transition

Question 3

Structure of Prostate (2 of 2)

_________ zone: behind transition zone
surrounds ejaculatory ducts
very few prostate cancers start in this zone

_______ ____________ _______: muscle fibres & fibrous connective tissue & doesn’t contain glands
——prostate cancer is rarely found in this part of prostate

Answer 3

Central

Anterior Fibromuscular Stroma

Question 4

Function of Prostate

produces ____ _________ ______:
-A thin, clear, alkaline fluid for semen
-added to and liquefies semen
-helps move sperm during ejaculation

Controls _______ flow
-urethra passes through the prostate

Answer 4

Prostate Specific Antigen

urine

Question 5

__________ _________ __________

is a protease
-cleave the high molecular weight protein of the seminal coagulum into smaller polypeptides
-this action results in the semen becoming less viscous.

Answer 5

PSA

Question 6

_________ _____
-is the best* method of detecting localized prostatic cancer and monitoring response to treatment

-However, it lacks specificity, as it is also increased in most patients with benign prostatic hyperplasia
(PSA is produced by epithelial prostatic cells, both benign and malignant.)

Answer 6

Serum PSA

Question 7

Dysfunction of Prostate (1 of 3)

1. ______________: inflammation of the tissue of the prostate gland
   -most common complaint of younger men
   -acute bacterial prostatitis can be the result of bacteria, a virus, or a sexually transmitted disease
   -difficult to treat (prostate is “isolated” from general circulation)
   -infection can start when bacteria in urine leak into the prostate
   -There’s no direct evidence that prostatitis can lead to prostate cancer

Symptoms
-Pain or burning sensation when urinating (dysuria)
-Difficulty urinating, such as dribbling or hesitant urination
-Frequent urination, particularly at night (nocturia)
-Cloudy or bloody urine
-Pain in the abdomen, groin or lower back

Answer 7

Prostatitis

Question 8

Dysfunction of Prostate (2 of 3)

2. ________ ____________ __________
   -common in men over 50
   -non-malignant enlargement of the prostate,
   -Not due to inflammation
   -condition characterized by growth of a benign tumor inside the prostate or prostate enlargement
   -Oral meds or may require a trans urethral resection of the prostate (TURP) to widen the urethral passage

Symptoms
-frequent or urgent need to urinate
-Increased frequency of urination at night (nocturia)
-Difficulty starting urination
-Weak urine stream or a stream that stops and starts
-Dribbling at the end of urination
-Inability to completely empty the bladder

Answer 8

Benign Prostatic Hyperplasia

Question 9

Dysfunction of Prostate (3 of 3)

3. ________ ____________:

-Many grow slowly and are confined to the prostate gland, where they may not cause serious harm.

-Prostate cancer metastasis occurs when cells break away from the tumor in the prostate. The cancer cells can travel through the lymphatic system or the bloodstream to other areas of the body. Most commonly prostate cancer metastasis can occur in the:
—Bones
—Lymph nodes
—Lungs
—Liver
—Brain

Answer 9

Prostate Cancer

Question 10

Prostate Cancer

Question 11

Prostate Cancer

Question 12

Biological markers

-prostate dysfunction (cancer) results in the release of some of its products into the blood stream
due to increased diffusion from tissue breakdown rather than increased production

-these products can be used to detect disease and are measured in the laboratory by drawing a blood sample

-two of these protein products are PAP (Prostatic Acid Phosphatase) and PSA, used as biological markers or tumour markers

Question 13

_______ _____ __________
-phosphatases are a group of enzymes that indiscriminately dephosphorylate a large variety of naturally occurring and synthetic substrates

-acid phosphatases show optimal activity at pH_____

-serum should be separated from red cells ASAP to prevent leakage of RBC and platelet AcP.

-rapidly deactivated in a blood sample
—-(↓ in CO2 results in an ↑ in pH): 50 % deactivation in 1 h at RT
—-stabilize by acidification to a pH
< 6.5, or (more commonly) freeze the serum if not assayed immediately

Answer 13

Prostatic Acid Phosphatase

Question 14

AcP Distribution & Characteristics

-acid phosphatases are widely distributed throughout the body: ___ specificity

-the prostate gland is the richest source of AcP (many times the activity of other tissue)
—–increased AcP often only detected when the tumour has metastasized: _____ sensitivity

-AcP activity also found in bone, liver, spleen, kidney and platelets, RBCs

-usefulness as a tumour marker depends upon ability to differentiate prostatic enzyme from non-prostatic enzyme

-Neither method of AcP determination is sensitive to prostatic carcinoma that has not metastasized, and only elevated in about 50% of the cases that have metastasized.

Answer 14

low

low

Question 15

How to separate AcP and PAP

Question 16

Problems with PAP (1 of 2)

Poor specificity***

-also elevated in other conditions
—anemia
—hyperparathyroidism
—heart attack
—kidney disease
—multiple myeloma
—bone malignancies
—other conditions

Question 17

Problems with PAP (2 of 2)

-Because of this severe lack of specificity:
—-unacceptable marker for monitoring post treatment because it has other sources
—-analytically unstable
—-large biological variation
—-positive predictive value <5%
(of no use in a screening population)
—-not useful in early-stage disease, when treatment would be most effective
—-CSCC Position Statement recommends discontinuing PAP testing

Question 18

______ ________ _________
-first identified and purified in 1979
-PSA in both normal and pathological tissue

-produced by prostate ductal epithelium of the seminal vesicles

-a serine protease (breaks down proteins at serine amino acid residues)

-normal function is to break down proteins (liquefaction) of the seminal coagulum to release spermatozoa

-Originally thought to be prostate specific, it has since been shown not to be the case

-occurs in several molecular forms including free (uncomplexed) forms
(PSA in seminal fluid is primarily free (uncomplexed))

-PSA in serum is primarily (__%) bound to proteinase inhibitors

-total PSA = combination of all immune detectable forms in serum

Answer 18

Prostate Specific Antigen

80

Question 19

PSA, cont’d

Why is most of serum PSA bound to proteinase inhibitors?

-Complexing inhibitors prevent PSA from digesting proteins in the blood

-PSA acts to break down proteins in the seminal coagulum to release spermatozoa.

-Most of the serum PSA is bound to proteinase inhibitors such as a1-antichymotrypsin in order to prevent it from acting on and breaking down serum proteins.

Question 20

Role of PSA measurement

Question 21

Screening

PSA testing is not sensitive enough to be used alone.
3 most commonly used tests:
1.
2.
3.

____ testing is superior; best in conjunction with DRE
—benefit in detecting earlier stage prostate cancer
—doubles detection rate of early cancer
—reasonable to expect decreased mortality

Answer 21

1. Digital Rectal Exam
2. Transrectal Ultrasound
3. PSA

PSA

Question 22

Diagnosis & Prognosis

Greatest value is in _______ stage disease

–PSA values correlate well with _____ (degree of spread) and _________ score (histopathological appearance) of prostate cancer

Answer 22

early

stage

Gleason

Question 23

BPH vs CaP

Question 24

BPH vs CaP

Question 25

Monitoring

____-_______ prostatectomy
—PSA should be undetectable within 1 to 3 months
—Hormone therapy: suppress testosterone: to shrink the prostate and the tumour before commencing radiotherapy

___-______ therapy
—mildly and transiently elevated several months before reaching baseline level

___-______ therapy
—typically within reference range
—increasing or persistently elevated PSA levels correlate with the probability of recurrent or residual disease

Answer 25

Post-Radical Prostatectomy

Post-Radiation therapy

Post-hormone therapy

Question 26

PSA Testing Method:

1. 2.

-bead coated with anti-PSA (capture) antibody
-PSA in patient sample binds to antibody
-second (detection) Ab, tagged with an enzyme or other label, binds to captured PSA to complete the sandwich
-signal measurement is directly proportional to concentration of PSA

Answer 26

1. Heterogeneous Sandwich Immunoassay
2. Immunoradiometric Assay (IRMA)

Question 27

Problems

Question 28

Problems

Question 29

Problems

Question 30

Problems

Question 31

Efforts to improve PSA specificity

PSA exists in two main forms in blood:
1.
2.

-_____ ___ test may be used to help determine whether biopsy should be done when total PSA is only slightly elevated

-Men with BPH tend to have ______ levels of free PSA and men with prostate cancer tend to have _______ amounts of free PSA

-A relatively low level of free PSA ________ chances that a cancer is present, even if the total PSA is not significantly elevated

Answer 31

1.bound to proteins
2. free (not bound)

FREE PSA

Higher; lower

increases

Question 32

Efforts to improve PSA specificity

-gold standard for diagnosing prostate cancer is the _______ ________

-biopsies used in follow up to positive PSA results can cause discomfort, anxiety, and sometimes complications

-some other tests have been developed to aid in decisions about whether to undergo biopsy

Answer 32

prostate biopsy

Question 33

Efforts to improve PSA specificity

proPSA:
-this test looks for a _______ of PSA
-may be produced by prostate cancer cells at a higher rate than ______ prostate cells

Answer 33

precursor
benign

Question 34

________ is an enlargement of the prostate due to a non-malignant tumour or inflammation. It is quite common in men over 50.

Answer 34

BPH

Question 35

BPH has been associated with ________ levels of circulating PSA as the result of this hypertrophic tissue, although levels are generally not as high as would be measured in cases of prostate cancer

Answer 35

increased