25 - Prostate Cancer

Question 1

Androgens

Answer 1

• Testosterone (produced by testis)
• Androstenedione (produced by adrenals)
• Dihydrotestosterone (made from testosterone by the prostate)

Question 2

No androgens

Answer 2

Prostate glandular cells will undergo
apoptosis

Question 3

Prostate carcinoma

Answer 3

• Mainly adenocarcinoma
• Most common cause of cancer in men, second most common cause of cancer death
• Heterogeneous disease

Question 4

Risk factors

Answer 4

• Increasing rate with age
• Ethnicity (rare in asians, highest in black)
• Family history
• Germine mutations in DNA repair genes (BRCA2, BRCA1)
• Dietary factors

Question 5

Serum PSA

Answer 5

• PSA is a protein made only in the prostate
• Produced by the secretory cells of the
  prostate glands, and also by prostate carcinoma cells
• In carcinoma PSA production is increased and tissue barriers between prostate glands and capillaries are disrupted, releasing more into the blood stream
• High rate of false positives

Question 6

Causes of elevated PSA

Answer 6

• Nodular hyperplasia
• Prostate carcinoma
• Prostatitis
• Perineal trauma

Question 7

Prostate carcinoma histology

Answer 7

• Infiltrative glands too small, crowded and too clear
• Absent basal cell layer
• Large nuclei
• Prominent nucleoli

Question 8

Gleason scoring

Answer 8

• Both primary and secondary pattern of tissue organisation identified
• Primary is most common tissue pattern seen in tumour, secondary is next most common

Question 9

Pattern 3

Answer 9

Single well formed glands infiltrating among normal glands

Question 10

Pattern 4

Answer 10

Fused glands, poorly formed glands

Question 11

Pattern 5

Answer 11

Sheets of cells, single cells, tumour necrosis

Question 12

Gleason score

Answer 12

Sum of the most predominant pattern + worst pattern in a core biopsy

Question 13

Other factors in path report

Answer 13

• Type and size of tumour
• Grade (Gleason score)
• Stage (TNM System)
• Perineural invasion
• Margins

Question 14

Treatment options

Answer 14

• Active surveillance (small volume)
• Surgery
• Radiation therapy
• Hormone therapy
• Chemotherapy

Question 15

Androgens in prostate carcinoma

Answer 15

• Necessary for prostate carcinoma growth and
  survival.
• Androgens bind to and activate the androgen receptor, which then stimulates the expression of specific genes that cause prostate cells to grow
• Hormone therapy blocks receptor via LHRH signalling

Question 16

Castration resistance

Answer 16

• Continue to grow even when androgen levels in the body are extremely low or undetectable
• Achieved through androgen receptor gene amplification or mutations

Question 17

Androgen receptor mutations

Answer 17

• Rendering the receptor responsive to alternate, non-androgen ligands like estrogen/progesterone
• Ligand-independent AR activation (“outlaw receptor”)
• Activation of alternative signalling pathways, bypassing the need for AR altogether