Address of Corresponding Author

Tumor Biol 2005;26:9-16 (DOI: 10.1159/000084181)

  Key Words

• Adipocyte-derived leucine aminopeptidase
• Angiogenesis
• Endometrial carcinoma
• Prognosis
• Renin-angiotensin system

  Abstract

Objective: It has recently been appreciated that a local autocrine or paracrine renin-angiotensin system (RAS) may exist in a number of tissues. Angiotensin II (AngII) is a potent RAS-derived vasoconstrictor peptide, and it is involved in tumor angiogenesis. We have cloned human adipocyte-derived leucine aminopeptidase (A-LAP), which degrades Ang II. This study investigated whether the expression of A-LAP, Ang II, angiotensin type I receptor (AT1R) and vascular endothelial growth factor (VEGF) correlates with clinicopathologic factors and prognosis in patients with endometrial endometrioid adenocarcinoma. Methods: Histologic sections of formalin-fixed, paraffin-embedded specimens from 94 primary endometrial carcinomas were stained for A-LAP, AngII, AT1R and VEGF using each antibody. Disease-free survival (DFS) and other clinicopathologic characteristics were analyzed according to the intensity of each staining. Results: Of 94 cases, 91 (96.8%) showed specific A-LAP immunostaining. A-LAP expression demonstrated negative correlations with myometrial invasion (p = 0.01) and vascular infiltration (p = 0.01). Of 94 cases, 77 (81.9%) showed specific AngII immunostaining. We found a positive correlation between AngII expression and surgical stage (p = 0.01). Of 94 cases, 56 (59.6%) showed specific AT1R immunostaining and 73 (77.7%) specific VEGF immunostaining. We found a positive correlation between VEGF expression and lymph node metastasis (p = 0.05). AngII and AT1R expression predicted a significantly poorer prognosis. Contrarily, A-LAP expression indicated a significantly more favorable prognosis in endometrial endometrioid adenocarcinoma patients. Multivariate analysis demonstrated that A-LAP expression (odds ratio, 0.12; 95% confidence interval, 0.025-0.618; p = 0.01) was an independent prognostic factor. Conclusions: In this study, we demonstrated the existence of local RAS and A-LAP in endometrial endometrioid adenocarcinoma as prognostic predictors of clinical outcome. These findings suggest that the assessment of RAS and A-LAP status provides clinically useful prognostic information in patients with endometrial carcinoma.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Kiyosumi Shibata
Department Obstetrics and Gynecology
Nagoya University Graduate School of Medicine
Tsurumai-cho 65, Showa-ku, Nagoya 466-8550 (Japan)
Tel. +81 52 744 2263, Fax +81 52 744 2268, E-Mail shiba@med.nagoya-u.ac.jp

  Article Information

Received: August 6, 2004
Accepted after revision: September 29, 2004
Published online: February 28, 2005
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 2, Number of References : 31