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ERG Status at the Margin Is Associated With Biochemical Recurrence After Radical Prostatectomy With Positive Surgical

Daniela C Salles1, Adrianna A Mendes1, Misop Han2

  • 1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|February 24, 2023
PubMed
Summary

Positive surgical margins in prostatectomy increase biochemical recurrence (BCR) risk. ERG-positive tumors at the margin, with or without PTEN loss, significantly elevate BCR risk, aiding adjuvant therapy decisions.

Keywords:
ERGKi-67PTENpositive surgical marginsprostate cancerradical prostatectomy

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Area of Science:

  • Urology
  • Oncology
  • Molecular Pathology

Background:

  • Positive surgical margins after radical prostatectomy correlate with an elevated risk of biochemical recurrence (BCR).
  • Prognostic variability in patients with positive margins suggests a need for molecular biomarkers to refine risk stratification.
  • Assessing biomarkers specifically within tumor tissue at the margin is crucial for accurate prognosis.

Purpose of the Study:

  • To investigate the prognostic value of PTEN, ERG, and Ki-67 expression in prostatectomy tumor tissue at positive surgical margins.
  • To determine if these molecular biomarkers can stratify BCR risk in patients with positive margins.
  • To evaluate the association of ERG and PTEN status with BCR risk, independent of clinicopathologic factors.

Main Methods:

  • A case-cohort design was employed, selecting 215 patients with positive margins from a larger cohort of 813 radical prostatectomy cases (2008-2017).
  • Tissue microarrays were constructed from tumors adjacent to positive margins and stained for PTEN, ERG, and Ki-67.
  • Cox proportional hazards models, weighted for the case-cohort design, were used for multivariable analysis, adjusting for CAPRA-S score, adjuvant radiation, and grade group.

Main Results:

  • ERG expression was detected in 38% of evaluable cases and was independently associated with a 2.4-fold increased risk of BCR (P = .012).
  • PTEN loss, present in 20% of cases, showed an association with BCR on univariable analysis but lost significance in multivariable models (P = .890).
  • ERG positivity, irrespective of PTEN status, improved the predictive model's concordance index from 0.827 to 0.847.

Conclusions:

  • In prostatectomy patients with positive surgical margins, ERG-positive tumors at the margin are associated with a significantly higher risk of BCR.
  • ERG status, assessed at the positive margin, may serve as a valuable biomarker for guiding decisions regarding adjuvant therapy.
  • PTEN status at the margin did not independently predict BCR risk after adjusting for clinicopathologic variables.