This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takahashi, Y. Articles by Hiraoka, N. Search for Related Content PubMed PubMed Citation Articles by Takahashi, Y. Articles by Hiraoka, N.

Prognostic Value of Tumor Architecture, Tumor-Associated Vascular Characteristics, and Expression of Angiogenic Molecules in Pancreatic Endocrine Tumors

Authors' Affiliations: ¹ Pathology Division, National Cancer Center Research Institute; ² Division of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan; and ³ Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

Requests for reprints: Nobuyoshi Hiraoka, Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Phone: 81-3-3542-2511; Fax: 81-3-3248-2463; E-mail: nhiraoka{at}gan2.res.ncc.go.jp.

Purpose: It is difficult to predict the biological behavior of pancreatic endocrine tumors (PETs). Our aim was to evaluate the prognostic significance of certain variables in PETs.

Experimental Design: The following variables were examined in 37 patients with PETs and then compared with other clinicopathologic characteristics: histologic tumor structure; microvessel density (MVD) measured by three different methods, including a unique method involving calculation of solid area MVD; endothelial proliferation; and the immunohistochemical expression of vascular endothelial growth factor-A and CXC chemokine CXCL-12. Intratumoral vascular structures were analyzed by double immunofluorescence using 30-µm-thick sections.

Results: The presence of focal and intensive solid growth of tumor cells (large solid nests; P = 0.003), low solid area MVD (P = 0.002), a high endothelial cell proliferation index (EPI; P = 0.005), and high expression of CXCL-12 in PET cells (P = 0.018) were significant unfavorable prognostic indicators. The predominant structure of the overall tumor histology and the expression of vascular endothelial growth factor-A did not separate aggressive PETs. In areas of focal solid growth, tumor-associated blood vessels had obviously low MVD and high EPI, and their structures were poorly formed with highly abnormal features, in comparison with other areas. High expression of CXCL-12 in tumor cells was significantly associated with variables representing tumor growth, hematogenous tumor spread, low MVD, high EPI, and the presence of large solid nests.

Conclusions: This study has provided novel findings on the prognostic features of tumor architecture and tumor-associated angiogenesis in PETs. CXCL-12 is the first candidate molecule in association with neoangiogenesis in PETs.

This article has been cited by other articles:

				T. R Halfdanarson, J. Rubin, M. B Farnell, C. S Grant, and G. M Petersen Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors Endocr. Relat. Cancer, June 1, 2008; 15(2): 409 - 427. [Abstract] [Full Text] [PDF]

				N. Kobayashi, N. Hiraoka, W. Yamagami, H. Ojima, Y. Kanai, T. Kosuge, A. Nakajima, and S. Hirohashi FOXP3+ Regulatory T Cells Affect the Development and Progression of Hepatocarcinogenesis Clin. Cancer Res., February 1, 2007; 13(3): 902 - 911. [Abstract] [Full Text] [PDF]