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

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

SN - 0020-7136

VL - 138

SP - 1777

EP - 1784

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 7

ER -