title: Angiogenesis-Related Markers and Prognosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer.
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.
  
  
  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.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.|Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: E M V
authors.initials: EM
authors.lastname: de Cuba
authors.affiliation: Department of Surgery, Catharina Ziekenhuis Eindhoven, Eindhoven, The Netherlands.
authors.forename: I H J T
authors.initials: IH
authors.lastname: de Hingh
authors.affiliation: Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: N R
authors.initials: NR
authors.lastname: Sluiter
authors.affiliation: Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Kwakman
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: V M H
authors.initials: VM
authors.lastname: Coupé
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J A M
authors.initials: JA
authors.lastname: Beliën
authors.affiliation: Department of Surgery, Catharina Ziekenhuis Eindhoven, Eindhoven, The Netherlands.
authors.forename: V J
authors.initials: VJ
authors.lastname: Verwaal
authors.affiliation: Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: W J H J
authors.initials: WJ
authors.lastname: Meijerink
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Delis-van Diemen
authors.affiliation: Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bonjer
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
authors.affiliation: Department of Surgical Oncology, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. e.tevelde@vumc.nl.|Department of General Surgery, Section of Surgical Oncology and Digestive Surgery, VU University Medical Center, Amsterdam, The Netherlands. e.tevelde@vumc.nl.
authors.forename: E A
authors.initials: EA
authors.lastname: Te Velde
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D043924:Angiogenesis Modulating Agents; D014408:Biomarkers, Tumor