Accession Number:

ADA592884

Title:

Evaluation of Androgen Receptor Function in Prostate Cancer Prognosis and Therapeutic Stratification

Descriptive Note:

Annual rept. 30 Sep 2012-29 Sep 2013

Corporate Author:

HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE BETHESDA MD

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

20.0

Abstract:

Although most prostate cancers are initially responsive to androgen ablation therapy, they become treatment resistant as tumor cells develop mechanisms to evade the treatment. Early knowledge of the androgen receptor dysfunctions will help in patient stratification for emerging therapeutic strategies. We proposed an approach for monitoring potential dysfunctions of the androgen receptor by measuring expression of a panel of genes directly regulated by androgen receptor. We examined human prostate cancer tissues surgery or diagnostic biopsy specimens at early stages of the disease and matched with longitudinal follow up data. Within the first reporting period we have completed the quality control of detecting PSAKLK3, PMEPA1, NKX3.1, ODC1, AMD1 and TMPRSS2-ERG genes in VCap cell culture model monitoring kinetic and dose response to androgen. In the second reporting period we have completed the qRT-PCR evaluation of in 77 patients by monitoring ERG, PSA, PMEPA1 and GAPDH levels. Also, we have completed the evaluation of 40 whole mounted sections of RP specimens by immunohistochemistry assessing AR, ERG, NKX3.1 and PSA proteins and compared the results to corresponding GeneCHip mRNA expression levels from the same tumor foci. The result indicated remarkable accuracy of the androgen regulated gene expression at mRNA levels performed better in prediction favorable outcomes in tumors with well differentiated morphology. By the completion of the proposed research we will provide a quantitative index of AR dysfunction for enhancing prognostic accuracy and to stratify patients for specific therapeutic approaches at early stages of prostate cancer treatment.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE