Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab
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Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab. / Eefsen, Rikke Løvendahl; Engelholm, Lars Henning; Willemoe, Gro L.; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans C; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin.
In: International Journal of Cancer, Vol. 138, No. 7, 01.04.2016, p. 1777-84.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab
AU - Eefsen, Rikke Løvendahl
AU - Engelholm, Lars Henning
AU - Willemoe, Gro L.
AU - Van den Eynden, Gert G
AU - Laerum, Ole Didrik
AU - Christensen, Ib Jarle
AU - Rolff, Hans C
AU - Høyer-Hansen, Gunilla
AU - Osterlind, Kell
AU - Vainer, Ben
AU - Illemann, Martin
N1 - © 2015 UICC.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Adenocarcinoma
KW - Aged
KW - Angiogenesis Inhibitors
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Bevacizumab
KW - Cell Proliferation
KW - Chemotherapy, Adjuvant
KW - Colorectal Neoplasms
KW - Denmark
KW - Endothelial Cells
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - Kaplan-Meier Estimate
KW - Liver Neoplasms
KW - Male
KW - Middle Aged
KW - Neoadjuvant Therapy
KW - Neovascularization, Pathologic
KW - Proportional Hazards Models
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/ijc.29904
DO - 10.1002/ijc.29904
M3 - Journal article
C2 - 26510166
VL - 138
SP - 1777
EP - 1784
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 7
ER -
ID: 164452887