Abstract
Background/Purpose
This study investigated vascular endothelial growth factor (VEGF) and flk-1 expression in hepatic metastases from colon carcinoma, and their associations with tumor angiogenesis, proliferation, and apoptosis.
Methods
Immunohistochemical studies were performed for VEGF/flk-1, Ki-67, p53, and bcl-2 expression, and microvessel density (MVD) in surgical specimens from 35 patients who underwent hepatectomy for colon cancer liver metastases between 1986 and 2001.
Results
VEGF and flk-1 were expressed mainly in the cytoplasm of tumor cells. High VEGF expression was associated with high flk-1 expression (P = 0.043). MVDs of less than 15 and 15 or more were found in 5 (14.3%) and 30 (85.7%) of 35 hepatic metastases, respectively. A Ki-67 index (KI) of 50% or more was detected in 33/35 (94.3%) of tumors, and 23 of these (65.7%) showed a KI of 85% or more. A KI of less than 50% was present in 2/35 (5.7%) of tumors. The expression of VEGF/flk-1 was related to elevated MVD (P ≤ 0.026). VEGF was also associated with an increased KI (P = 0.025). Mutant p53 and bcl-2 expressions were detected in 26/35 (74.3%) and 17/35 (48.6%) of liver metastases, respectively. Mutant p53 was not related to VEGF/flk-1 expression, but bcl-2 was highly associated with flk-1 (P = 0.007). The incidences of high flk-1 expression and a KI of 85% or more were significantly higher in tumors which were both p53- and bcl-2-positive (93.3% and 73.3%) than in tumors which were negative for both (42.9% and 14.3%; P ≤ 0.021).
Conclusions
The VEGF-flk-1 system takes part in tumor angiogenesis, proliferation, and apoptosis in colon liver metastases. The bcl-2 pathway may upregulate VEGF activity via the flk-1 receptor. These findings are preliminary, requiring a larger sampling in order to elucidate the role of VEGF/flk-1 in metastatic colon cancer.
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Presented at the 89th Annual Clinical Congress of the American College of Surgeons, Chicago, IL, USA, October 19–23, 2003.
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Cheng, J., Slavin, R., Gallagher, J. et al. Expression of vascular endothelial growth factor and receptor flk-1 in colon cancer liver metastases. J Hepatobiliary Pancreat Surg 11, 164–170 (2004). https://doi.org/10.1007/s00534-003-0883-2
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DOI: https://doi.org/10.1007/s00534-003-0883-2