EAU 2017: Comprehensive molecular dissection of multi-focal prostate cancer and concomitant lymph node metastasis: Implications for tissue based prognostic biomarkers

London, England (UroToday.com) Current tissue based prognostic biomarker assays claim that genetic assessment of a single focus is sufficient to predict disease behaviour. The investigators of this study analyzed and compared the genetic profiles of multifocal prostate cancer patients with concordant lymph node metastasis (LNM) to determine if expression based prognostic tests are robust to multi-focality.

This study comprised patients after radical prostatectomy with pathology showing either an N1 disease or discordant multifocal disease. DNA and RNA were co-isolated from each tumor focus pre-identified on formalin fixed paraffin embedded specimens. For a total of 15 patients high depth, targeted DNA and RNA next generation sequencing was performed to characterize the genetic and transcriptional signature of each sample.

All primary tumor areas and LNM foci (along with control tissue when available) from 15 patients were analyzed. Significant intra- and inter-patient molecular heterogeneity was observed. By targeted RNAseq, low-grade and high-grade tumors from the same patient showed distinct expression profiles.

These results demonstrate that multifocal prostate cancer exhibits molecular heterogeneity, suggesting independent clonal origin and metastatic potential. Different alteration and expression profile in indolent and very aggressive foci in the same patient challenge the robustness of expression based prognostic tests. Additional molecular studies are needed to better characterize the biologically dominant nodule and improved prognostic biomarkers should be developed.

Speaker: Salami S., Hovelson D., Mathieu R., Kaplan J., Susani M., Rioux-Leclercq N., Shariat S., Tomlins S., Palapattu G.
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto

at the #EAU17 - March 24-28, 2017- London, England