Possible involvement of adipocyte-derived leucine aminopeptidase via angiotensin II in endometrial carcinoma.

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.

• Authors: Kiyosumi Shibata, Fumitaka Kikkawa, Yayoi Mizokami, Hiroaki Kajiyama, Kazuhiko Ino, Seiji Nomura, Shigehiko Mizutani
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) 2005 Jan-Feb Vol. 26 Issue 1 Pg. 9-16 ISSN: 1010-4283 [Print] Netherlands
• PMID: 15741767 (Publication Type: Journal Article)

Chemical References

• Receptor, Angiotensin, Type 1
• Vascular Endothelial Growth Factors
• Angiotensin II
• Leucyl Aminopeptidase

Topics

• Adipocytes (enzymology)
• Angiotensin II (analysis, biosynthesis)
• Carcinoma, Endometrioid (blood supply, metabolism, therapy)
• Disease-Free Survival
• Endometrial Neoplasms (blood supply, metabolism, therapy)
• Female
• Humans
• Leucyl Aminopeptidase (analysis, biosynthesis, genetics)
• Lymphatic Metastasis
• Middle Aged
• Neovascularization, Pathologic
• Receptor, Angiotensin, Type 1 (analysis, biosynthesis)
• Renin-Angiotensin System
• Vascular Endothelial Growth Factors (analysis, biosynthesis)