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PLoS By Category | Recent
PLoS Articles
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Urology
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A Tri-Marker Proliferation Index Predicts Biochemical Recurrence
after Surgery for Prostate Cancer
Published:
Monday, May 23, 2011
Author:
Sameer Malhotra et al.
by Sameer Malhotra, Jacques Lapointe, Keyan Salari, John P. Higgins, Michelle Ferrari, Kelli Montgomery, Matt van de Rijn, James D. Brooks, Jonathan R. Pollack
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.
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