EURURO Vol. 72 No. 5

675 860

Platinum Priority – Editorial
Referring to the article published on pp. 665–674 of this issue
Convergence of Genomic Instability and SChLAP1: Weathering
the Storm of Intraductal Carcinoma of the Prostate
Daniel E. Spratt
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Histopathology findings have single-handedly been the
most dominant prognostic biomarker in localized prostate
cancer for more than half a century. Only recently have
prognostic genomic biomarkers demonstrated an ability to
independently improve discriminatory and prognostic
performance above and beyond phenotypic Gleason pat-
terns . However, Gleason patterns are not the only
histopathology findings that represent intrinsic biological
and prognostic information.
Intraductal carcinoma (IDC) is another important patho-
logic finding that was originally described in 1973 How-
ever, for several decades IDC was largely forgotten, as it was
merely viewed as a histopathologic subtype without
prognostic relevance, and in fact was eventually grouped
with high-grade prostatic intraepithelial neoplasia in 1987
. Fortunately, we now know that the presence of IDC is
associated with an unfavorable prognosis, as demonstrated
across multiple independent studies Furthermore, IDC
is frequently associated with cribriform architecture (CA),
another subpathology that also portends a less favorable
prognosis . However, biological inquiry into these
unfavorable phenotypes is largely lacking, with many
unanswered questions that Chua and colleagues have
begun to unravel in this issue of European Urology.
The authors compiled one of the largest and most
rigorously analyzed multi-institutional cohorts (-
n = 932 with outcomes data) to assess the clinical and
biological impact of IDC for men with localized prostate
cancer. They included 211 patients (23%) who had IDC/CA
present. Similar to others, they found that IDC/CA presence
was associated with a two- to threefold higher rate of
biochemical failure, and a fourfold higher rate of metastasis.
To better understand the biological differences and
potentially identify a molecular fingerprint of IDC/CA+
tumors, the authors investigated percentage genome
aberration (PGA), hypoxia, and mRNA abundance. To little
surprise, PGA was significantly greater in patients with IDC/
CA present, fitting with the knowledge that tumors with IDC
[2_TD$DIFF]or genomic instability possess greater metastatic potential.
Furthermore, PGA remained an independent predictor of
metastasis in addition to IDC/CA, prostate-specific antigen,
grade, and T stage, raising the question of when genomic
instability occurs in the evolution of IDC. Therefore,
although genomic instability is more common in IDC/CA,
it is clearly not the sole explanation for the negative
prognostic impact of IDC. In addition, the added discrimi-
natory value PGA added to the model including IDC/CA in
predicting biochemical failure (c-index 0.74 vs 0.75) or
metastasis (c-index 0.79 vs 0.80) is probably of minimal
clinical relevance.
The authors next investigated hypoxia, which rather
than a tumor-specific feature like PGA, is an example of a
field-wide effect. It has been shown that a hypoxic
microenvironment is correlated with tumor invasion and
metastasis. In addition, hypoxia-inducible factor 1 is more
commonly overexpressed in metastases than in primary
tumors . Chua et al demonstrated an increase in hypoxia
for IDC/CA+
[1_TD$DIFF] tumors (64.0% vs 45.5%). However, the
difference was not statistically significant (p = 0.17), per-
haps because of the smaller sample size for these analyses
(n = 102). Furthermore, the authors did not demonstrate
that tumor hypoxia was independently associated with
negative outcomes in this data set or added clinical utility in
identifying a more aggressive phenotype above and beyond
merely the presence of IDC/CA. Therefore, it is difficult to
ava ilable at
journal homepage:
DOI of original article: .
* Department of Radiation Oncology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0010, USA.
Tel. +1 734 6471372; Fax: +1 734 9361900.
0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.