Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer

Sci Rep. 2019 Sep 19;9(1):13579. doi: 10.1038/s41598-019-49964-7.


Prostate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci are present at primary diagnosis. Molecular classification of prostate cancer can potentially aid the precision of diagnosis and treatment. A promising genomic classifier was published by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate cancers into seven groups based on one cancer sample per patient. Here, we explore the clinical usefulness of this classification by testing the classifier's performance in a multifocal context. We analyzed 106 cancer samples from 85 distinct cancer foci within 39 patients. By somatic mutation data from whole-exome sequencing and targeted qualitative and quantitative gene expression assays, 31% of the patients were uniquely classified into one of the seven TCGA classes. Further, different samples from the same focus had conflicting classification in 12% of the foci. In conclusion, the level of both intra- and interfocal heterogeneity is extensive and must be taken into consideration in the development of clinically useful molecular classification of primary prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Exome Sequencing
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Genetic Heterogeneity*
  • Humans
  • Male
  • Mutation*
  • Prostatic Neoplasms / classification*
  • Prostatic Neoplasms / genetics