Antibody-based detection of ERG rearrangements in prostate core biopsies, including diagnostically challenging cases: ERG staining in prostate core biopsies

Arch Pathol Lab Med. 2012 Aug;136(8):935-46. doi: 10.5858/arpa.2011-0424-OA.

Abstract

Context: Fusions of androgen-regulated genes and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) occur in approximately 50% of prostate cancers, encoding a truncated ERG product. In prostatectomy specimens, ERG rearrangements are greater than 99% specific for prostate cancer or high-grade prostatic intraepithelial neoplasia adjacent to ERG-rearranged prostate cancer by fluorescence in situ hybridization and immunohistochemistry.

Objective: To evaluate ERG staining by immunohistochemistry on needle biopsies, including diagnostically challenging cases.

Design: Biopsies from a retrospective cohort (n = 111) enriched in cores requiring diagnostic immunohistochemistry and a prospective cohort from all cases during 3 months (n = 311) were stained with an anti-ERG antibody (clone EPR3864).

Results: Among evaluable cores (n = 418), ERG staining was confined to cancerous epithelium (71 of 160 cores; 44%), high-grade prostatic intraepithelial neoplasia (12 of 68 cores; 18%), and atypical foci (3 of 28 cores; 11%), with staining in only 2 of 162 cores (1%) diagnosed as benign. The ERG was expressed in about 5 morphologically benign glands across 418 cores and was uniformly expressed by all cancerous glands in 70 of 71 cores (99%).

Conclusions: ERG staining is more prostate cancer-specific than α-methylacyl-coenzyme A racemase, and staining in an atypical focus supports a diagnosis of cancer if high-grade prostatic intraepithelial neoplasia can be excluded. Thus, ERG staining shows utility in diagnostically challenging biopsies and may be useful in molecularly subtyping prostate cancer and in stratifying isolated high-grade prostatic intraepithelial neoplasia by risk of subsequent cancer.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antibody Specificity
  • Biopsy, Needle
  • Cohort Studies
  • Epithelium / metabolism
  • Epithelium / pathology
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Prospective Studies
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Intraepithelial Neoplasia / diagnosis
  • Prostatic Intraepithelial Neoplasia / genetics
  • Prostatic Intraepithelial Neoplasia / metabolism
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Retrospective Studies
  • Sensitivity and Specificity
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Regulator ERG

Substances

  • ERG protein, human
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcriptional Regulator ERG