Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.
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.
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Rikke Løvendahl
RL
Eefsen
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Lars
L
Engelholm
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Gro L
GL
Willemoe
GZA Hospitals St.Augustinus, Translational Cancer Research Unit, Antwerp, Belgium.
Gert G
GG
Van den Eynden
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, the Gade Laboratory of Pathology, University of Bergen, Norway.
Ole Didrik
OD
Laerum
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Ib Jarle
IJ
Christensen
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Department of Surgery, Rigshospitalet, Copenhagen, Denmark.
Hans Christian
HC
Rolff
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Gunilla
G
Høyer-Hansen
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Kell
K
Osterlind
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Ben
B
Vainer
The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Martin
M
Illemann
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D003718:Denmark; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D016016:Proportional Hazards Models
D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
Ki67; angiogenesis; colorectal cancer; growth pattern; liver metastasis; microvessel density