title: Versican and vascular endothelial growth factor expression levels in peritoneal metastases from colorectal cancer are associated with survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
abstract: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can increase survival of colorectal cancer (CRC) patients with peritoneal metastases (PM). This treatment is associated with high morbidity and mortality rates. Therefore, improvement of patient selection is necessary. Assuming that the clinical phenotype is dictated by biological mechanisms, biomarkers could play a crucial role in this process. Since it is unknown whether and to what extent angiogenesis influences the course of disease in patients with PM, we investigated the expression of two angiogenesis-related markers and their relation to overall survival (OS) in CRC patients after CRS and HIPEC. Clinicopathological data and tissue samples were collected from 65 CRC patients with isolated metastases to the peritoneum that underwent CRS and HIPEC. Whole tissue specimens from PM were evaluated for versican (VCAN) expression, VEGF expression and microvessel density (MVD) by immunohistochemistry. The relation between these markers and OS was assessed using univariate and multivariate analysis. Associations between VEGF expression, VCAN expression, MVD and clinicopathological data were tested. High stromal VCAN expression was associated with high MVD (p = 0.001), better resection outcome (p = 0.003) and high T-stage (p = 0.027). High epithelial VCAN expression was associated with MVD (p = 0.007) and a more complete resection (p < 0.001). In multivariate analysis, simplified peritoneal cancer index (p = 0.001), VEGF expression levels (p = 0.012), age (p = 0.030), epithelial VCAN expression levels (p = 0.042) and lymph node status (p = 0.053) were associated with OS. Concluding, VCAN and VEGF were associated with survival in CRC patients with PM after CRS and HIPEC. Independent validation in a well-defined patient cohort is required to confirm the putative prognostic role of these candidate biomarkers.
authors.affiliation: Section of Surgical Oncology and Digestive Surgery, Department of General Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: N R
authors.initials: NR
authors.lastname: Sluiter
authors.affiliation: Section of Surgical Oncology and Digestive Surgery, Department of General Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.|Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: E M V
authors.initials: EM
authors.lastname: de Cuba
authors.affiliation: Section of Surgical Oncology and Digestive Surgery, Department of General Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Kwakman
authors.affiliation: Section of Surgical Oncology and Digestive Surgery, Department of General Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: W J H J
authors.initials: WJ
authors.lastname: Meijerink
authors.affiliation: Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Delis-van Diemen
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: V M H
authors.initials: VM
authors.lastname: Coupé
authors.affiliation: Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.|Department of Pathology, NKI-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: J A M
authors.initials: JA
authors.lastname: Beliën
authors.affiliation: Department of Pathology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.|Department of Pathology, NKI-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
authors.affiliation: Department of Surgery, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.
authors.forename: I H J T
authors.initials: IH
authors.lastname: de Hingh
authors.affiliation: Section of Surgical Oncology and Digestive Surgery, Department of General Surgery, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. e.tevelde@vumc.nl.
authors.forename: E A
authors.initials: EA
authors.lastname: te Velde
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D065426:Cytoreduction Surgical Procedures; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006979:Hyperthermia, Induced; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D053675:Versicans / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C508322:VCAN protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053675:Versicans
keywords: Angiogenesis; Biomarkers; Colorectal cancer; HIPEC; Peritoneal metastases; VEGF; Versican