A tri-marker proliferation index predicts biochemical recurrence after surgery for prostate cancer. Academic Article uri icon

Overview

abstract

  • Prostate cancer exhibits tremendous variability in clinical behavior, ranging from indolent to lethal disease. Better prognostic markers are needed to stratify patients for appropriately aggressive therapy. By expression profiling, we can identify a proliferation signature variably expressed in prostate cancers. Here, we asked whether one or more tissue biomarkers might capture that information, and provide prognostic utility. We assayed three proliferation signature genes: MKI67 (Ki-67; also a classic proliferation biomarker), TOP2A (DNA topoisomerase II, alpha), and E2F1 (E2F transcription factor 1). Immunohistochemical staining was evaluable on 139 radical prostatectomy cases (in tissue microarray format), with a median clinical follow-up of eight years. Each of the three proliferation markers was by itself prognostic. Notably, combining the three markers together as a "proliferation index" (0 or 1, vs. 2 or 3 positive markers) provided superior prognostic performance (hazard ratio = 2.6 (95% CI: 1.4-4.9); P = 0.001). In a multivariate analysis that included preoperative serum prostate specific antigen (PSA) levels, Gleason grade and pathologic tumor stage, the composite proliferation index remained a significant predictor (P = 0.005). Analysis of receiver-operating characteristic (ROC) curves confirmed the improved prognostication afforded by incorporating the proliferation index (compared to the clinicopathologic data alone). Our findings highlight the potential value of a multi-gene signature-based diagnostic, and define a tri-marker proliferation index with possible utility for improved prognostication and treatment stratification in prostate cancer.

authors

  • Malhotra, Sameer
  • Lapointe, Jacques
  • Salari, Keyan
  • Higgins, John P
  • Ferrari, Michelle
  • Montgomery, Kelli
  • van de Rijn, Matt
  • Brooks, James D
  • Pollack, Jonathan R

publication date

  • May 23, 2011

Research

keywords

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • E2F1 Transcription Factor
  • Ki-67 Antigen
  • Neoplasm Recurrence, Local
  • Prostatic Neoplasms

Identity

PubMed Central ID

  • PMC3100337

Scopus Document Identifier

  • 79956363107

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0020293

PubMed ID

  • 21629784

Additional Document Info

volume

  • 6

issue

  • 5