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18 Cards in this Set

  • Front
  • Back
What are the most common alterations seen in prostate cancer genetics?
To date, the most common molecular events in prostate cancer involve androgen receptor (AR) mutation or amplification,(29-31) gene rearrangements of ETS transcription factors, (5) and loss of PTEN.

Advancing Precision Medicine for Prostate Cancer Through Genomics. JCO, 2013.
How common are the ETS gene fusion products in prostate cancer?
A prevalence of 50% of prostate
cancers.

Advancing Precision Medicine for Prostate Cancer Through Genomics. JCO, 2013.
Are androgen receptor genetic alterations seen even in patients with metastatic castrate resistant prostate cancer?
Current data on prostate cancer genomics suggest more than 50% of metastatic CRPCs display AR amplification or mutation (9)

Advancing Precision Medicine for Prostate Cancer Through Genomics. JCO, 2013.
What is PCA3? Is it expressed anywhere besides the prostate?
Non-coding RNA transcript assoc w/ CaP. The gene that encodes this transcript is on Chr 9 and is 4 exons long. RNA transcript is expressed only in the prostate.

Memory aids - assoc/ w/ other biomarkers of CaP - PSA, PCA3, pro-PSA, pPSA, PHI, freePSA, TMPRSS2 fusion protein...could also assoc/ w/ other biomarkers in general...CEA (colon & ovarian Ca), MUC-1 (colon)
How does one test for PCA3?
Cancerous cells from the prostate are shed into the urine and have high expression levels of PCA3 in comparison to normal prostate tissue. So one gets 20-30mls of urine after a DRE.

The quantitative PCA3 score was then developed which references the PCA3 mRNA/PSA mRNA level as a ratio then x 1000....this normalizes your PCA3 level to PSA. As you could expect a high value means you are at higher risk for CaP.

Molecular Dx of CaP. J Urol 2012.
What is the average sensitivity and specificity of PCA3 for prostate cancer detection?
Sensitivity ~66%
Specificity ~ 76%

reference to PSA - Specificty ~47%

Molecular Dx of CaP. J Urol 2012.
Has PCA3 been included in any nomograms?
This is a note card that would need to be constantly updated but as of this writing yes there are nomograms including PCA3 with PSA and if you look at Thompson's PCPT trial prostate risk calculator you can add in PCA3.
What is the most common specific fusion protein associated with prostate cancer?
TMPRSS2:ERG fusion protein. - title stands for transmembrane protease serine 2.
What is the ability of the TMPRSS2:ERG fusion protein to predict prostate cancer as a biomarker test?
It's PPV is amazing. 90% specificity and 94% PPV. It is also a urine test.
What is currently the only approved molecular marker for prostate cancer?
It is PCA3.
Is PCA3 over-expressed in all prostate cancers?
It isn't all prostate cancers but it is estimated that 95% of prostate cancers over-express PCA3 in comparison to normal prostate tissue.

Molecular Dx of CaP. J Urol 2012
How well does PCA3 perform in terms of PPV and NPV for prostate biopsy?
Table found in Molecular Dx of CaP.  J Urol, 2012
Table found in Molecular Dx of CaP. J Urol, 2012
Could PCA3 have any value in predicting strategies for men on active surveillance or considering active surveillance?
In a recently published study Auprich et al assessed
the clinical staging significance of PCA3 score.(23) PCA3 scores were significantly lower in men with low volume tumors and insignificant PCa, corroborating
the findings of Nakanishi et al.(20) The study confirmed that PCA3 score fulfills the criterion of being a valuable predictor of low volume,
insignificant cancer and could be of great help for
selecting patients with PCa who are candidates for
active surveillance.

Molecular Dx of CaP. J Urol 2012.
What are some of the characteristics that make PCA3 similar and different than PSA?
*Both are specific for the prostate and are not produced by other tissues
*PCA3 is not affected by age or prostate size
*PCA3 is not affected by 5 alpha reductase inhibitors
*PCA3 is not affected by amount of previous biopsies or prostate inflammation.
Since both are urine tests have people combined the PCA3 test and the TMPRSS2:ERG fusion protein test at the same time?
There was one study listed in this review where they were combined to improve the sensitivty, which increased to around 75%, the specificity was still very good.

Molecular Dx CaP. J Urol, 2012
What is the IMPACT trial for prostate cancer?
This is a multinational trial that is accruing through countries like the UK to assess the relative risk or genetic risk to patients of BRCA1 and BRCA2 mutations as to their risk of prostate cancer and aggressive prostate cancer....not sure when it is set to come out but the accrual is well under way.
Do patients with BRCA1 or BRCA2 mutations in general have a different histology?
There were many studies that said no, however a study in 2010 in CCR from the MSK group showed that for a gropu of Ashkenazi Jews those with a BRCA2 mutation were more likely to have GG 8 or higher disease compared to non-carriers or BRCA1 carriers.
-Germline BRCA Mutations Denote a Clinicopathologic Subset of CaP. CCR 2010
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