Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab

Research output: Contribution to journalJournal articleResearchpeer-review

  • Rikke Løvendahl Eefsen
  • Engelholm, Lars Henning
  • Gro L. Willemoe
  • Gert G Van den Eynden
  • Ole Didrik Laerum
  • Ib Jarle Christensen
  • Hans C Rolff
  • Gunilla Høyer-Hansen
  • Kell Osterlind
  • Ben Vainer
  • Martin Illemann

The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p < 0.0001). Microvessel density was decreased in liver metastases from patients treated with bevacizumab in comparison to those from untreated/chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect.

Original languageEnglish
JournalInternational Journal of Cancer
Volume138
Issue number7
Pages (from-to)1777-84
Number of pages8
ISSN0020-7136
DOIs
Publication statusPublished - 1 Apr 2016

    Research areas

  • Adenocarcinoma, Aged, Angiogenesis Inhibitors, Antineoplastic Combined Chemotherapy Protocols, Bevacizumab, Cell Proliferation, Chemotherapy, Adjuvant, Colorectal Neoplasms, Denmark, Endothelial Cells, Female, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Liver Neoplasms, Male, Middle Aged, Neoadjuvant Therapy, Neovascularization, Pathologic, Proportional Hazards Models, Journal Article, Research Support, Non-U.S. Gov't

ID: 164452887