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

Overview

Journal Ann Surg Oncol

Publisher Springer

Specialty Oncology

Date 2016 Jan 6

PMID 26727921

Citations 10

Authors

E M V de Cuba

I H J T de Hingh

N R Sluiter

R Kwakman

V M H Coupe

J A M Belien

V J Verwaal

W J H J Meijerink

P M Delis-van Diemen

H J Bonjer

G A Meijer

E A te Velde

Affiliations

Soon will be listed here.

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.

Citing Articles

Impact of Molecular Status on Cytoreductive Surgery for Peritoneal Metastases from Colorectal Cancer.

Zhong Y, Yang K, Qin X, Luo R, Wang H Clin Colon Rectal Surg. 2023; 36(6):415-422.

PMID: 37795471 PMC: 10547537. DOI: 10.1055/s-0043-1767705.

Treatment and Survival Outcomes for Patients with Colorectal Peritoneal Metastases Deemed Ineligible for Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Results of a Retrospective Study.

Dietz M, Ziekman M, van Kooten J, Brandt-Kerkhof A, van Meerten E, Verhoef C Ann Surg Oncol. 2022; 30(4):2048-2056.

PMID: 36566258 DOI: 10.1245/s10434-022-12969-0.

Tumor expression of CXCL12 and survival of patients with colorectal cancer: A meta-analysis.

Zhang S, Li G Oncol Lett. 2022; 24(6):436.

PMID: 36420080 PMC: 9641825. DOI: 10.3892/ol.2022.13556.

New insights in the pathology of peritoneal surface malignancy.

Carr N J Gastrointest Oncol. 2021; 12(Suppl 1):S216-S229.

PMID: 33968439 PMC: 8100698. DOI: 10.21037/jgo-2020-01.

Colorectal Peritoneal Metastases: A Systematic Review of Current and Emerging Trends in Clinical and Translational Research.

Koumpa F, Xylas D, Konopka M, Galea D, Veselkov K, Antoniou A Gastroenterol Res Pract. 2019; 2019:5180895.

PMID: 31065262 PMC: 6466888. DOI: 10.1155/2019/5180895.

References

Blancher C, Moore J, Talks K, Houlbrook S, Harris A . Relationship of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression to vascular endothelial growth factor induction and hypoxia survival in human breast cancer cell lines. Cancer Res. 2001; 60(24):7106-13. View

Shaheen R, Ahmad S, Liu W, Reinmuth N, Jung Y, Tseng W . Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors. Br J Cancer. 2001; 85(4):584-9. PMC: 2364099. DOI: 10.1054/bjoc.2001.1936. View

Harris A . Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer. 2002; 2(1):38-47. DOI: 10.1038/nrc704. View

Beasley N, Leek R, Alam M, Turley H, Cox G, Gatter K . Hypoxia-inducible factors HIF-1alpha and HIF-2alpha in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res. 2002; 62(9):2493-7. View

Dvorak H . Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002; 20(21):4368-80. DOI: 10.1200/JCO.2002.10.088. View

Verwaal V, van Ruth S, de Bree E, van Sloothen G, van Tinteren H, Boot H . Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003; 21(20):3737-43. DOI: 10.1200/JCO.2003.04.187. View

Verwaal V, Zoetmulder F . Follow-up of patients treated by cytoreduction and chemotherapy for peritoneal carcinomatosis of colorectal origin. Eur J Surg Oncol. 2004; 30(3):280-5. DOI: 10.1016/j.ejso.2003.12.003. View

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

Sugarbaker P . Peritonectomy procedures. Ann Surg. 1995; 221(1):29-42. PMC: 1234492. DOI: 10.1097/00000658-199501000-00004. View

10.

Zebrowski B, Liu W, Ramirez K, Akagi Y, Mills G, Ellis L . Markedly elevated levels of vascular endothelial growth factor in malignant ascites. Ann Surg Oncol. 1999; 6(4):373-8. DOI: 10.1007/s10434-999-0373-0. View

11.

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

12.

McShane L, Altman D, Sauerbrei W, Taube S, Gion M, Clark G . REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005; 93(4):387-91. PMC: 2361579. DOI: 10.1038/sj.bjc.6602678. View

13.

Koppe M, Boerman O, Oyen W, Bleichrodt R . Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg. 2006; 243(2):212-22. PMC: 1448921. DOI: 10.1097/01.sla.0000197702.46394.16. View

14.

Hong X, Jiang F, Kalkanis S, Zhang Z, Zhang X, deCarvalho A . SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion. Cancer Lett. 2005; 236(1):39-45. DOI: 10.1016/j.canlet.2005.05.011. View

15.

Bird N, Mangnall D, Majeed A . Biology of colorectal liver metastases: A review. J Surg Oncol. 2006; 94(1):68-80. DOI: 10.1002/jso.20558. View

16.

Gerber S, Rybalko V, Bigelow C, Lugade A, Foster T, Frelinger J . Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth. Am J Pathol. 2006; 169(5):1739-52. PMC: 1780209. DOI: 10.2353/ajpath.2006.051222. View

17.

Yoshikawa T, Tsuburaya A, Miyagi Y, Sekiguchi H, Kimura M, Cho H . Up-regulation of hypoxia-inducible factor-1 alpha and VEGF mRNAs in peritoneal dissemination of patients with gastric cancer. Anticancer Res. 2006; 26(5B):3849-53. View

18.

Chandler B, Detsika M, Khoo S, Williams J, Back D, Owen A . Factors impacting the expression of membrane-bound proteins in lymphocytes from HIV-positive subjects. J Antimicrob Chemother. 2007; 60(3):685-9. DOI: 10.1093/jac/dkm230. View

19.

Varghese S, Burness M, Xu H, Beresnev T, Pingpank J, Alexander H . Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum. Ann Surg Oncol. 2007; 14(12):3460-71. DOI: 10.1245/s10434-007-9557-7. View

20.

Furlan D, Sahnane N, Carnevali I, Cerutti R, Uccella S, Bertolini V . Up-regulation and stabilization of HIF-1alpha in colorectal carcinomas. Surg Oncol. 2007; 16 Suppl 1:S25-7. DOI: 10.1016/j.suronc.2007.10.014. View