TMPRSS2-ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features

Samson W. Fine, Anuradha Gopalan, Margaret A. Leversha, Hikmat A. Al-Ahmadie, Satish K. Tickoo, Qin Zhou, Jaya M. Satagopan, Peter T. Scardino, William L. Gerald, Victor E. Reuter

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

TMPRSS2-ERG gene rearrangement is seen in about half of clinically localized prostate cancers, yet controversy exists with regard to its prognostic implications. Similarly, the relationship of TMPRSS2-ERG fusion to Gleason score and morphology remains uncertain. We assigned Gleason scores and recorded morphological features for 521 clinically localized prostate cancers sampled in triplicate and arrayed in eight tissue microarray blocks. Fluorescence in situ hybridization was performed to delineate TMPRSS2-ERG aberrations. Using maximum Gleason score, based on three core evaluation, and overall Gleason score, based on prostatectomy sections, Fisher's exact test was performed for tumors with TMPRSS2-ERG translocation/deletion, copy number increase (≥3) of the TMPRSS2-ERG region without translocation/deletion, and copy number increase and concomitant translocation/deletion. In all, 217 (42%) translocation/deletion and 30 (5.9%) copy number increase-alone cases were detected. Among 217 translocation/deletion cases, 32 had translocation/deletion with copy number increase. In all, 237, 200, and 75 cancers had maximum core-specific Gleason score of 6, 7, and 8-10, respectively. Tumors with translocation/deletion tended toward lower Gleason scores than those without (P<0.002) with similar results for overall Gleason score (P<0.02); copy number increase cases tended toward higher Gleason scores than those without (p<0.001). Gleason score of 8-10 tumors demonstrated lower odds of translocation/deletion (odds ratio (OR) 0.38; 95% CI 0.21-0.68) and higher odds of copy number increase alone (OR 7.33; 95% CI 2.65-20.31) or copy number increasetranslocation/deletion (OR 3.03; 95% CI 1.12-8.15) relative to Gleason score of 7 tumors. No significant difference in TMPRSS2-ERG incidence was observed between patients with and without cribriform glands, glomerulations, signet-ring cells, or intraductal cancer (P0.821, 0.095, 0.132, 0.375). TMPRSS2-ERG gene fusion is associated with lower core-specific and overall Gleason scores and not with high-grade morphologies. Conversely, TMPRSS2-ERG copy number increase, with or without rearrangement, is associated with higher Gleason score. These findings indicate that translocation/deletion of TMPRSS2-ERG is not associated with histological features of aggressive prostate cancer.

Original languageEnglish (US)
Pages (from-to)1325-1333
Number of pages9
JournalModern Pathology
Volume23
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Keywords

  • ERG
  • Fusion
  • Gleason score
  • Morphology
  • Prostate cancer
  • TMPRSS2

Fingerprint

Dive into the research topics of 'TMPRSS2-ERG gene fusion is associated with low Gleason scores and not with high-grade morphological features'. Together they form a unique fingerprint.

Cite this