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Related Concept Videos

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Multifocal Electroretinograms
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Transcriptomic heterogeneity in multifocal prostate cancer.

Simpa S Salami1,2, Daniel H Hovelson3, Jeremy B Kaplan3

  • 1Department of Urology, Michigan Medicine, Ann Arbor, Michigan, USA.

JCI Insight
|November 3, 2018
PubMed
Summary
This summary is machine-generated.

Commercial gene expression assays for prostate cancer may not accurately reflect aggressive disease when multifocal tumors are present. Low-grade biopsy results might miss coexisting higher-grade cancer, impacting clinical decisions.

Keywords:
CancerMolecular diagnosisOncologyProstate cancer

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Diagnostics

Background:

  • Commercial gene expression assays aid prostate cancer treatment decisions, especially for active surveillance.
  • Prostate cancer's heterogeneity necessitates assays robust to multifocal disease for clinical utility.
  • This study evaluates transcriptomic profiles in multifocal prostate cancer to assess assay robustness.

Purpose of the Study:

  • To assess the robustness of commercial gene expression assays in the context of multifocal prostate cancer.
  • To determine if prognostic signatures are reliable when low-grade and high-grade cancer coexist within the same prostate.
  • To evaluate the clinical utility of current assays for guiding active surveillance decisions in multifocal prostate cancer cases.

Main Methods:

  • A multiplexed targeted RNA-sequencing assay was developed to assess multiple transcriptional classes.
  • The assay was applied to a retrospective cohort of 156 prostate cancer samples from multiple institutions.
  • Commercial prognostic signatures (Prolaris, Genomic Prostate Score, Decipher) were derived and compared across different tumor foci.

Main Results:

  • Derived gene expression scores correlated positively with tumor grade (rS = 0.53-0.73, P < 0.001).
  • In cases with extreme grade discordance (GG1 and ≥GG4), scores were significantly lower in low-grade (GG1) versus high-grade (≥GG4) foci (P < 0.001).
  • No significant difference in scores was found between GG1 foci from prostates with and without coexisting higher-grade cancer (P > 0.05).

Conclusions:

  • Multifocal prostate cancer exhibits distinct prognostic expression signatures between low-grade and high-grade foci.
  • Prognostic RNA expression assays on low-grade biopsy tissue may not detect coexisting aggressive disease.
  • Current assays may require re-evaluation for reliability in multifocal prostate cancer management.