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

de Cuba, E M V ; de Hingh, I H J T ; Sluiter, N R ; Kwakman, R ; Coupé, V M H ; Beliën, J A M ; Verwaal, V J LU ; Meijerink, W J H J ; Delis-van Diemen, P M and Bonjer, H J , et al. (2016) In Annals of Surgical Oncology 23(5). p.1601-1608
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
keywords
Adenocarcinoma/metabolism, Adenocarcinoma, Mucinous/metabolism, Angiogenesis Modulating Agents/metabolism, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/metabolism, Carcinoma, Signet Ring Cell/metabolism, Chemotherapy, Adjuvant, Chemotherapy, Cancer, Regional Perfusion, Colorectal Neoplasms/metabolism, Combined Modality Therapy, Cytoreduction Surgical Procedures, Female, Follow-Up Studies, Humans, Hyperthermia, Induced, Immunoenzyme Techniques, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Neovascularization, Pathologic/prevention & control, Peritoneal Neoplasms/metabolism, Prognosis, Prospective Studies, Survival Rate
in
Annals of Surgical Oncology
volume
23
issue
5
pages
1601 - 1608
publisher
Springer
external identifiers
  • scopus:84952908178
  • pmid:26727921
ISSN
1534-4681
DOI
10.1245/s10434-015-5023-0
language
English
LU publication?
no
id
655dfd8d-e1a6-47ee-94f2-ce0f9e060f2c
date added to LUP
2022-04-05 09:38:18
date last changed
2024-03-21 11:43:03
@article{655dfd8d-e1a6-47ee-94f2-ce0f9e060f2c,
  abstract     = {{<p>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.</p><p>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.</p><p>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 &lt; 0.01, P &lt; 0.01, and P = 0.02, respectively). However, no association was found between the other markers and OS (P &gt; 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).</p><p>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.</p>}},
  author       = {{de Cuba, E M V and de Hingh, I H J T and Sluiter, N R and Kwakman, R and Coupé, V M H and Beliën, J A M and Verwaal, V J and Meijerink, W J H J and Delis-van Diemen, P M and Bonjer, H J and Meijer, G A and Te Velde, E A}},
  issn         = {{1534-4681}},
  keywords     = {{Adenocarcinoma/metabolism; Adenocarcinoma, Mucinous/metabolism; Angiogenesis Modulating Agents/metabolism; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Biomarkers, Tumor/metabolism; Carcinoma, Signet Ring Cell/metabolism; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Colorectal Neoplasms/metabolism; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Follow-Up Studies; Humans; Hyperthermia, Induced; Immunoenzyme Techniques; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic/prevention & control; Peritoneal Neoplasms/metabolism; Prognosis; Prospective Studies; Survival Rate}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1601--1608}},
  publisher    = {{Springer}},
  series       = {{Annals of Surgical Oncology}},
  title        = {{Angiogenesis-Related Markers and Prognosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer}},
  url          = {{http://dx.doi.org/10.1245/s10434-015-5023-0}},
  doi          = {{10.1245/s10434-015-5023-0}},
  volume       = {{23}},
  year         = {{2016}},
}