Angiogenesis-Related Markers and Prognosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer.

E M V De Cuba,P M Delis-Van Diemen,E A Te Velde,H J Bonjer,G A Meijer,R Kwakman,J A M Beliën,W J H J Meijerink,I H J T De Hingh,N R Sluiter,V J Verwaal,V M H Coupé

doi:10.1245/s10434-015-5023-0

E M V De Cuba, P M Delis-Van Diemen + Show 10 more

Open Access

https://doi.org/10.1245/s10434-015-5023-0

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Journal: Annals of surgical oncology	Publication Date: Jan 4, 2016
Citations: 17	License type: CC BY 4.0

Affiliation: Amsterdam UMC Location VUmc

Abstract

BackgroundPatients presenting with peritoneal metastases (PM) of colorectal cancer (CRC) can be curatively treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Angiogenesis is under control of multiple molecules of which HIF1a, SDF1, CXCR4, and VEGF are key players. We investigated these angiogenesis-related markers and their prognostic value in patients with PM arising from CRC treated with CRS and HIPEC.Patients and MethodsClinicopathological data and tissue specimens were collected in 2 tertiary referral centers from 52 patients who underwent treatment for isolated PM of CRC. Whole tissue specimens were subsequently analyzed for protein expression of HIF1a, SDF1, CXCR4, and VEGF by immunohistochemistry. Microvessel density (MVD) was analyzed by CD31 immunohistochemistry. The relationship between overall survival (OS) and protein expression as well as other clinicopathological characteristics was analyzed.ResultsUnivariate analysis showed that high peritoneal cancer index (PCI), resection with residual disease and high expression of VEGF were negatively correlated with OS after treatment with CRS and HIPEC (P < 0.01, P < 0.01, and P = 0.02, respectively). However, no association was found between the other markers and OS (P > 0.05). Multivariate analysis showed an independent association between OS and PCI, resection outcome and VEGF expression (multivariate HR: 6.1, 7.8 and 3.8, respectively, P ≤ 0.05).ConclusionsAn independent association was found between high VEGF expression levels and worse OS after CRS and HIPEC. The addition of VEGF expression to the routine clinicopathological workup could help to identify patients at risk for early treatment failure. Furthermore, VEGF may be a potential target for adjuvant treatment in these patients.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-015-5023-0) contains supplementary material, which is available to authorized users.

Highlights

Patients presenting with peritoneal metastases (PM) of colorectal cancer (CRC) can be curatively treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
Formalin-fixed and paraffin-embedded (FFPE) tissue specimens obtained during CRS were collected from the archives and hematoxylin-eosin (H&E) slides were reviewed to verify the presence of tumor cells
An association was noted between a high HIF1a expression and favorable resection outcome (p = 0.03) and male gender and higher CXCR4 expression (p = 0.01) No association was seen between expression levels of HIF1a, CXCR4, SDF1, Vascular endothelial growth factor (VEGF), and Microvessel density (MVD) with the clinicopathological characteristics listed in Table 1 (p [ 0.05, data not shown)

Summary

Introduction

Patients presenting with peritoneal metastases (PM) of colorectal cancer (CRC) can be curatively treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Results

Conclusion