Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2015; 21(22): 6924-6930
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6924
Prognostic angiogenic markers (endoglin, VEGF, CD31) and tumor cell proliferation (Ki67) for gastrointestinal stromal tumors
Rodrigo Panno Basilio-de-Oliveira, Vera Lucia Nunes Pannain
Rodrigo Panno Basilio-de-Oliveira, Pathology Post-Graduate Program, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil
Rodrigo Panno Basilio-de-Oliveira, Department of Pathology and Clinical Support, Federal University of Rio de Janeiro State, 22280-110 Rio de Janeiro, Brazil
Vera Lucia Nunes Pannain, Department of Pathology, Pathology Post-Graduate Program, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil
Author contributions: Basilio-de-Oliveira RP and Nunes Pannain VL contributed equally to this article; both designed the study, performed the research, analyzed the data, wrote the paper, and revised the final version to be published.
Ethics approval: The Ethics Committee of the research of the University Hospital Clementino Fraga Filho under No. 079/05.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: None of the authors of this study has received fees for serving as a speaker, a consultant and/or an advisory board member. None has received research funding from organization(s).
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at rodrigopboliveira@gmail.com. Participant gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Rodrigo Panno Basilio-de-Oliveira, Associate Professor, Department of Pathology and Clinical Support, Federal University of Rio de Janeiro State, Street Alvaro Ramos 71/505, Rio de Janeiro 22280-110, Brazil. rodrigopboliveira@gmail.com
Telephone: +55-212-2041365 Fax: +55-212-5695605
Received: December 20, 2015
Peer-review started: December 21, 2015
First decision: January 22, 2015
Revised: February 23, 2015
Accepted: March 30, 2015
Article in press: March 31, 2015
Published online: June 14, 2015
Abstract

AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor (VEGF)], proliferative index (Ki67), and prognosis of patients with gastrointestinal stromal tumors (GIST).

METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients’ demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin (CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density (IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF, Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5% positive cells. The prognosis was classified as good (patient alive without recurrence) or poor (patient with recurrence/death).

RESULTS: The distribution of tumor sites among the 54 analyzed samples was as follows: 27 (50%) in the stomach, 20 (37.1%) in the small intestine, 6 (11.1%) in the colon, and 1 (1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm (median: 8 cm); in 12 cases (22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases (77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis (P < 0.001). The cut-off values of CD105 (> 1.2%) and CD31 (> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis. Cases with a better prognosis showed significantly null/weak staining for VEGF (P < 0.001). Ki-67 expression of ≥ 5% was strongly correlated with a worse prognosis (P < 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis.

CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.

Keywords: Angiogenesis, Immunohistochemistry, CD105, CD31, Gastrointestinal stromal tumors, Vascular endothelial growth factor, Ki-67

Core tip: Prognosis of gastrointestinal stromal tumors (GIST) is a longstanding challenge. Association of angioimmunomarkers with poor prognosis has recently been demonstrated, but few studies have evaluated the relevance of vascular endothelial growth factor (VEGF) and CD31, and none has analyzed the role of CD105 expression in prognosis. Our results suggest that angiogenic markers (intratumoral microvascular density cut-off of CD105 and CD31 besides VEGF) and Ki67 (tumor cell proliferation marker), may be prognostic factors for GIST, besides and Ki67 (tumor cell proliferation). However, further studies are necessary before considering such angiogenic molecules as possible therapeutic targets.