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. 2016 May;23(5):1601-8.
doi: 10.1245/s10434-015-5023-0. Epub 2016 Jan 4.

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

E M V de Cuba  1   2 , I H J T de Hingh  3 , N R Sluiter  1 , R Kwakman  1 , V M H Coupé  4 , J A M Beliën  2 , V J Verwaal  3 , W J H J Meijerink  1 , P M Delis-van Diemen  2 , H J Bonjer  1 , G A Meijer  2   5 , E A Te Velde  6   7
Affiliations

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

E M V de Cuba et al. Ann Surg Oncol. 2016 May.

Abstract

Background: Patients 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 methods: Clinicopathological 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.

Results: Univariate 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).

Conclusions: An 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.

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Figures

Fig. 1
Fig. 1
Expression pattern of a HIF1a, b SDF1, c CXCR4, and d VEGF staining in peritoneal metastases of colorectal cancer epithelium. Immunohistochemical staining patterns ranged from weak to strong epithelial (nucleus and cytoplasm) staining for all 4 markers. Representative examples of all stainings, ranging from weak (1) to strong (3) in peritoneal metastases epithelium are shown
Fig. 2
Fig. 2
Kaplan-Meier curves showing the correlation between high and low expression of respectively, a HIF1a, b SDF1, c CXCR4, d VEGF, and e MVD and overall survival in patients undergoing curative CRS and HIPEC for the treatment of PM of CRC
See this image and copyright information in PMC

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