T. Suzuki et al., Imbalance between neutral endopeptidase 24.11 and endothelin-1 expression in human endometrial carcinoma, ONCOL-BASEL, 60(3), 2001, pp. 258-267
Objectives: Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptid
ase that degrades various bioactive peptides including endothelin-l (ET-1).
This enzyme is known to play a role in maintaining ET-l-regulated vascular
homeostasis in the normal human endometrium. The purpose of the present st
udy was to investigate the expression and localization of NEP and ET-1 in n
eoplastic endometria, and also to clarify the correlation of their expressi
on with the tumor grade of endometrial carcinoma. Methods: Immunohistochemi
cal analysis for NEP and ET-1 expression was performed on paraffin-embedded
tissue sections of 7 normal endometria (after menopause), 5 atypical endom
etrial hyperplasias (AEH), and 32 endometrial endometrioid adenocarcinomas.
Results: In normal endometrium and AEH, NEP immunoreactivity was detected
in stromal cells, but not in glandular cells. In contrast, ET-1 immunoreact
ivity was detected in both glandular and stromal cells. In the stromal cell
s of grade 1 endometrial adenocarcinoma, NEP was detected at high or modera
te quantities. However, significantly decreased NEP immunoreactivity was ob
served in the stromal cells of grade 2 and 3 adenocarcinomas. However, NEP
was not immunostained in adenocarcinoma cells except for the lesions of squ
amous differentiation. ET-1 immunoreactivity was weakly detected in the str
omal cells of grade 1 adenocarcinoma, but the intensity of ET-1 staining in
creased with advancing tumor grade. The ratio of the staining scores of str
omal ET-1 to stromal NEP was positively correlated with the tumor grade. Co
nclusions: These findings demonstrate that NEP expression in the stromal ce
lls of endometrial adenocarcinoma is downregulated, while stromal ET-1 is u
pregulated, with increasing tumor grade. The present findings also suggest
that NEP may play a role in the regulation of neoplastic transformation, tu
mor progression, and differentiation in endometrial neoplasms, possibly by
degrading certain peptide growth factors such as ET-1. Copyright (C) 2001 S
. Karger AG, Basel.