Am. De Marzo et al., E-cadherin expression as a marker of tumor aggressiveness in routinely processed radical prostatectomy specimens, UROLOGY, 53(4), 1999, pp. 707-713
Objectives. Approximately 30% of clinically localized prostate adenocarcino
mas treated by radical prostatectomy (RP) will recur within 10 years. To pr
event recurrence, new adjuvant therapies are in development that seek to tr
eat high-risk patients after surgery. To identify patients as candidates fo
r these treatments, improved biomarkers for predicting prognosis are needed
. Reduced expression of E-cadherin has been proposed as a new marker for pr
edicting prognosis in prostate adenocarcinoma. Since few studies have exami
ned the relation between risk factors for disease progression and E-cadheri
n expression using routinely processed RP specimens, we used RP specimens t
o correlate downregulation of E-cadherin and pathologic stage at RP.
Methods. Primary adenocarcinomas (n = 76) from formalin-fixed and paraffin-
embedded RP specimens were evaluated by immunohistochemistry against E-cadh
erin (HECD-1) using heat-induced epitope retrieval and automated staining (
BioTek Solutions). Normal appearing prostate epithelium was used as an inte
rnal control for each specimen. Staining was scored as an estimate of the p
ercentage of tumor cells in each specimen that showed strong plasma membran
e staining.
Results. Specimens were divided into three categories with respect to Gleas
on score: intermediate (score 5 to 6, n = 31), intermediate to high (score
7, n = 25), and high (score 8 to 9, n = 20). For pathologic stage, specimen
s were divided into three categories: low stage/organ confined (pT2, n = 30
), intermediate stage/ limited extraprostatic extension (pT3a, n = 25), and
high stage/seminal vesicle-pelvic lymph node metastases (pT3b-any pTN1, n
= 21). In univariate analysis, reduced levels of E-cadherin correlated with
advanced Gleason score (P = 0.003) and advanced pathologic stage (P = 0.00
8). In multivariate analysis, E-cadherin, preoperative prostate-specific an
tigen, and Gleason score all contributed independently to the prediction of
high-stage disease (P <0.0001). Ten pelvic lymph node metastases from this
same patient cohort were stained for E-cadherin. All were positive and 9 o
f 10 were moderately to strongly positive.
Conclusions, Since essentially all patients in the high-stage category have
a very high likelihood of disease recurrence, we conclude that the study o
f E-cadherin in a prospective manner as a potential biomarker of disease pr
ogression in patients with clinically organ-confined prostate cancer who un
dergo RP is warranted. Additionally, our finding that most metastatic tumor
cells in pelvic lymph nodes express E-cadherin supports the notion that th
e establishment of the distant colonization and growth of metastatic tumor
cells may be facilitated by expression or re-expression of previously downr
egulated E-cadherin. This would strongly suggest that irreversible genetic
inactivation through mutation or allelic loss at 16q2.3 is probably not the
mechanism of E-cadherin downregulation in most abnormally expressing prima
ry prostate carcinomas. (C) 1999, Elsevier Science Inc. All rights reserved
.