Efficient, high-resolution measurement of telomeres in archival tissue specimens for use in personalized medicine

C15079 Efficient, high-resolution measurement of telomeres in archival tissue specimens for use in personalized medicine
 
Unmet Need
Current prognostic indicators do not adequately predict prostate cancer behavior, particularly in men with clinically-localized disease. New molecular markers, beyond the currently used indicators (i.e., pathologic stage, Gleason score and PSA concentration at diagnosis), are urgently needed to help with prostate cancer treatment.
 
Located at the ends of chromosomes, telomeres are repetitive DNA elements that protect the chromosomes from degradation and abnormal genetic recombination, thus helping maintain the integrity of the genome. Studies suggest that reduced telomere length in prostate-cancer associated stromal cells coupled with variability in telomere length among prostate cancer cells is associated with poor clinical outcome in prostate cancer patients, including progression to prostate cancer death independent of currently prognostic indicators. Measurement of telomere length may be useful as a new molecular biomarker for prostate cancer prognosis.
 
Technology Overview
Hopkins researchers have developed a high-throughput method to quantitate cell type-specific telomere lengths at single cell resolution in archival, formalin-fixed paraffin-embedded (FFPE) prostate tissues. This method is sufficiently robust and reproducible to detect biologically significant differences in telomere lengths in prostate biopsies or prostatectomy specimens, either on whole slide or on tissue microarray format, and may be readily translated into other tissue types. These telomere measurements may be utilize for improved prognostication and/or risk stratification, allowing for individualize therapeutic strategies to increase the benefit-to-risk ratio for men, and reduce healthcare costs associated with prostate cancer.
 
Stage of Development
The semi-automated approach are based on performing microscope slide-based, telomere-specific fluorescence in situ hybridization (FISH) combined with multiplex immunofluorescence detecting basal cell-specific, epithelial cell-specific and lymphocyte-specific markers using FFPE tissue samples. Cell-type specific telomere and nuclear DNA content data are obtain from collected microscopic images and analyzed with digital image analysis software.
 
Clinical data are available.

 
Publications
Meeker AK et al. Telomere length assessment in human archival tissues: combined telomere fluorescence in situ hybridization and immunostaining. Am J Pathol. 2002 Apr;160(4):1259-68.
 
Heaphy CM et al. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discov. 2013 Oct;3(10):1130-41.
 

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