Chapter 149 Prostate Cancer Biomarkers

Question 1

What kallikrein activates proPSA to mature PSA?

Answer 1

hK2 (human kallikrein 2).

Question 2

PSA bound to α2-macroglobulin (A2M) — is it measurable?

Answer 2

No — it’s masked from immunoassays, though still enzymatically

Question 3

Does recent DRE meaningfully elevate PSA?

Answer 3

No — any rise is clinically insignificant.

Question 4

Percent-free PSA level suggesting low cancer risk?

Answer 4

A: >25%.

Question 5

Normal annual PSA rise in men without BPH?

Answer 5

0.04 ng/ml/year

Question 6

free PSA includes

Answer 6

ProPSA, BPSA, Intact PSA

Question 7

Serum PSA bound to A1-antichymotrypsin accounts for

Answer 7

60-90% of SERUM PSA

Question 8

kallikrein family gene cluster location is PSA (hK3) part of?

Answer 8

Chromosome 19q13.2–q13.4

Question 9

Which molecular form of PSA is enzymatically active but undetectable by most immunoassays?

Answer 9

PSA–A2M

Question 10

PSA’s main role is

Answer 10

degrade Semenogelin/ fibronectin

Question 11

Facilitate the development and validation of ASsays

Answer 11

BRLs

Question 12

SA–API accounts for how % of total serum PSA

Answer 12

1-5%

Question 13

Why use %fPSA

Answer 13

Problem: Total PSA (especially 4–10 ng/mL) overlaps heavily between benign and malignant prostate conditions → leads to many unnecessary biopsies.

Solution: %fPSA helps distinguish cancer (more complexed PSA, less free PSA) from benign conditions (higher proportion of free PSA).

Question 14

Using %fPSA improve

Answer 14

→ Sensitivity for detecting cancer: ~70–95%, depending on cutoff.
→ Specificity (avoiding unnecessary biopsies): 20–65%.

Practical gain: Avoiding ~20–65% of unnecessary biopsies while still detecting most cancers.

Question 15

%fPSA best used when total PSA is

Answer 15

4-10 ng/ml

Question 16

likelihood ratio reviewer

Answer 16

LR⁺ > 10 → strong increase in disease probability.

LR⁺ ~5 → moderate increase.

LR ~1 → no change.

LR⁻ < 0.1 → strong decrease in disease probability.

LR⁻ ~0.2 → moderate decrease.

Question 17

AUC under the Receiver Operating characteristic Curve, what is a perfect test, and useless test

Answer 17

1.0 is perfect test
0.5 is useless(random)
other values:
0.9–1.0 → excellent.
0.8–0.9 → good
0.7–0.8 → fair
0.6–0.7 → poor

Question 18

Inactive precursor form , mechanism for activation

Answer 18

pro-PSA,N-terminal blocking the active site –> Activated by hK2

Question 19

Once PSA is in the bloodstream, it is inactivated by

Answer 19

Binding to A1-antichymotrypsin (ACT), a2-macroglobulin A2M, small amounts binds to a1-protease inhibitor (API)

Question 20

Only ~5–45% of circulating PSA remains unbound (free PSA, fPSA) , which includes

Answer 20

Intact PSA, BPSA, proPSA

Question 21

proPSA subtype strongly associatef with PCa

Answer 21

[-2]proPSA

Question 22

what is intact PSA

Answer 22

full length, unprocessed PSA molecule, circulating in the free PSA pool

Question 23

what blood test combines PSA, fPSA, [-2] pro PSA to improive specificity?

Answer 23

PHI

Question 24

formula to calculate PHI

Answer 24

[-2] proPSA/PSA x square of PSA

Question 25

compared to PSA or %fPSA alone, what does PHI improve

Answer 25

specificity for GS 7 PCa

Question 26

what is PSMA, where is it expressed, and what are the molecular imaging?

Answer 26

type II transmembrane glycoprotein highly expressed on prostate epithelial cells. 68Ga-PSMA PET/CT or 18F-PSMA PET: → Extremely sensitive for detecting recurrent/metastatic disease, even at very low PSA levels (<0.2 ng/mL).

Question 27

four-kalikrein panel, utility

Answer 27

Total PSA, free PSA, intact PSA, hK2 predicts high grade PCa on biopsy

Question 28

What is Cellsearch

Answer 28

Captures Circulating Tumor Cells using EpCAM, and stains for CK

Question 29

What is circulating tumor DNA (ctDNA)?

Answer 29

A: Fragments of tumor-derived DNA in plasma, used for liquid biopsy to detect mutations and monitor treatment.

Question 30

what is the only FDA Approved CTC detection system

Answer 30

CellsEARCH (EpCAM, cytokeratin and CD45)

Question 31

prognostic CTC cutoff in mCRPC?

Answer 31

>5 ctcs per 7.5 ml blood, poor survical marker

Question 32

What is AR-V7, and where is it detected?

Answer 32

Androgen REceptor Splice Variant 7, it is detected in CTCs and associated with resistance to Androgen pathway inhibtors

Question 33

AR V7 positive CTCs predict resistance to which drugs

Answer 33

Abi and enza

Question 34

What therapy is favored in AR V7 Posiitive mCRPC patients?

Answer 34

Taxane based chemo (doce, cabazi)

Question 35

PCA3

Answer 35

A long noncoding RNA highly overexpressed in PCa, detectable in urine

Question 36

FDA approved cutoff for PCA3

Answer 36

25

Question 37

Gene fusion is present in 50% of PSA screened cancers?

Answer 37

TMPRESS2:ERG fusion

Question 38

How does combining PCA3+TMPRESS2:ERG affect diagnostic accuracy?

Answer 38

improves AUC 0.80 to 0.84 reducing unncessarry biopsies

Question 39

Mi-PRostate Score combines what?

Answer 39

Serum PSA, urine PCA3 and TMPRESS2:ERG

Question 40

mRNA biomarkers in SelectMDx test

Answer 40

HOXC6 and DLX1 mRNA

Question 41

repeat biopsy setting, what is the negative predictve value of NPV of PCA3 <20?

Answer 41

~88%

Question 42

family of molecules does Annexin A3 belong to?

Answer 42

Calcium and Phospholipid-binding protein

Question 43

How do annexin A3 level in urine relate to prostate cancer risk?

Answer 43

Lower annexin A3 leves are associated with higher cancer reisk

Question 44

AUC for Annexin A3 + PSA for predicting biopsy outcomes?

Answer 44

0,81

Question 45

multiplex panel included annexin A3?

Answer 45

PCA3+ TMPRESS2:ERG+ ANNEXIN a3 + Sarcosine

Question 46

what are mirnas?

Answer 46

small noncoding RNAs (19-22 nt) that regulate mRNA expression

Question 47

urinary miRNA is an indenpendent predictor of prostate cancer at bipsy

Answer 47

miR-187

Question 48

Epigenetics

Answer 48

Heritable changes in gene expression that do not involve alterations to the DNA sequence

Question 49

Molecular process underlies most epigenetic gene silencing in prostate cancer

Answer 49

Promoter hypermethylation of CpG islands

Question 50

Most frequently hypermethylated in prostate cancer

Answer 50

GSTP1 Gluthatione S transferase P1

Question 51

How does GSTP1 hypermethylation contribute to cancer development

Answer 51

reduces detoxfication capacity leading to increased dna damage

Question 52

name 2 other genes commonly showing promoter hypermethylation in PCa

Answer 52

RARB2 and RASSF1A

Question 53

On which chromosome is the AMACR gene located?

Answer 53

Chromosome 5

Question 54

what is the biological function of AMACR

Answer 54

B-oxidation of branched chain fatty acids

Question 55

how is AMACR used diagnostically in PCa

Answer 55

IHC on biopsy

Question 56

what is the prognostic implication of decreased AMACR staining

Answer 56

increased risk of PCa progression

Question 57

which urine biomarker guides repeat biopsy decisions, esp after prior negative biopsy?

Answer 57

PCA 3 (long noncoding RNA, improves specificty over PSA)

Question 58

what multiplex urine test combines PSA, PCA3, TMPRESS2:ERG gene fusion

Answer 58

MiPs

Question 59

urine mrna test includes HOXc6 and DLX1 to predict high grade ancer

Answer 59

selectMDX

Question 60

genomic tissue test using 31 ccp + 15 housekeeping genes to predict recurrence?

Answer 60

Prolaris

Question 61

Tissue test that preducts adverse pathology Gleason >4, pT3, to guide surveillance decisions

Answer 61

Oncotype DX prostate

Question 62

tissue test predicting mets and guides post-surgery radiation decisions

Answer 62

decipher

Question 63

inherited mutations to increase PCa risk via Homologous recombination defects?

Answer 63

BRCA1, BRCA2, chek2, ATM

Question 64

which inherited syndrome involving MSH2 raises PCa cancer risk 10 fold

Answer 64

Lynch syndrome