OBJECTIVE: Resection of a primary colorectal carcinoma (CRC) can be accompanied by rapid outgrowth of liver metastases, suggesting a role for angiogenesis. The aim of this study is to investigate whether the presence of a primary CRC is associated with changes in angiogenic status and proliferation/apoptotic rate in synchronous liver metastases and/or adjacent liver parenchyma. METHODS: Gene expression and localization of CD31, HIF-1α, members of the vascular endothelial growth factor (VEGF) and Angiopoietin (Ang) system were studied using qRT-PCR and immunohistochemistry in colorectal liver metastases and nontumorous-adjacent liver parenchyma. Proliferation and apoptotic rate were quantified. Three groups of patients were included: (1) simultaneous resection of synchronous liver metastases and primary tumor (SS-group), (2) resection of synchronous liver metastases 3 to 12 months after resection of the primary tumor [late synchronous (LS-group)], and (3) resection of metachronous metastases >14 months after resection of the primary tumor (M-group). RESULTS: In all 3 groups a higher expression of the angiogenic factors was encountered in adjacent liver parenchyma as compared to the metastases. VEGFR-2 gene expression was abundant in adjacent liver parenchyma in all 3 groups. VEGF-A and VEGFR-1 were prominent in adjacent parenchyma in the SS-group. The SS-group showed the highest Ang-2/Ang-1 ratio both in the metastases and the adjacent liver. This was accompanied by a high turnover of tumor cells. CONCLUSION: In the presence of the primary tumor, the liver parenchyma adjacent to the synchronous liver metastases provides an angiogenic prosperous environment for metastatic tumor growth.
OBJECTIVE: Resection of a primary colorectal carcinoma (CRC) can be accompanied by rapid outgrowth of liver metastases, suggesting a role for angiogenesis. The aim of this study is to investigate whether the presence of a primary CRC is associated with changes in angiogenic status and proliferation/apoptotic rate in synchronous liver metastases and/or adjacent liver parenchyma. METHODS: Gene expression and localization of CD31, HIF-1α, members of the vascular endothelial growth factor (VEGF) and Angiopoietin (Ang) system were studied using qRT-PCR and immunohistochemistry in colorectal liver metastases and nontumorous-adjacent liver parenchyma. Proliferation and apoptotic rate were quantified. Three groups of patients were included: (1) simultaneous resection of synchronous liver metastases and primary tumor (SS-group), (2) resection of synchronous liver metastases 3 to 12 months after resection of the primary tumor [late synchronous (LS-group)], and (3) resection of metachronous metastases >14 months after resection of the primary tumor (M-group). RESULTS: In all 3 groups a higher expression of the angiogenic factors was encountered in adjacent liver parenchyma as compared to the metastases. VEGFR-2 gene expression was abundant in adjacent liver parenchyma in all 3 groups. VEGF-A and VEGFR-1 were prominent in adjacent parenchyma in the SS-group. The SS-group showed the highest Ang-2/Ang-1 ratio both in the metastases and the adjacent liver. This was accompanied by a high turnover of tumor cells. CONCLUSION: In the presence of the primary tumor, the liver parenchyma adjacent to the synchronous liver metastases provides an angiogenic prosperous environment for metastatic tumor growth.
Authors: C Lim; A Doussot; M Osseis; F Esposito; C Salloum; J Calderaro; C Tournigand; D Azoulay Journal: Clin Transl Oncol Date: 2018-03-28 Impact factor: 3.405
Authors: Constantinos Simillis; Eliana Kalakouti; Thalia Afxentiou; Christos Kontovounisios; Jason J Smith; David Cunningham; Michel Adamina; Paris P Tekkis Journal: World J Surg Date: 2019-07 Impact factor: 3.352
Authors: Amber L Simpson; Alexandre Doussot; John M Creasy; Lauryn B Adams; Peter J Allen; Ronald P DeMatteo; Mithat Gönen; Nancy E Kemeny; T Peter Kingham; Jinru Shia; William R Jarnagin; Richard K G Do; Michael I D'Angelica Journal: Ann Surg Oncol Date: 2017-05-30 Impact factor: 5.344
Authors: Louis de Mestier; Gilles Manceau; Cindy Neuzillet; Jean Baptiste Bachet; Jean Philippe Spano; Reza Kianmanesh; Jean Christophe Vaillant; Olivier Bouché; Laurent Hannoun; Mehdi Karoui Journal: World J Gastrointest Oncol Date: 2014-06-15
Authors: Mariya B Aksenenko; Nadezhda V Palkina; Olga N Sergeeva; Ekaterina Yu Sergeeva; Andrey K Kirichenko; Tatiana G Ruksha Journal: Int J Exp Pathol Date: 2020-02-11 Impact factor: 1.925
Authors: Ajith K Siriwardena; James M Mason; Saifee Mullamitha; Helen C Hancock; Santhalingam Jegatheeswaran Journal: Nat Rev Clin Oncol Date: 2014-06-03 Impact factor: 66.675