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10.1245/s10434-008-9811-7
Annals of Surgical Oncology 15:1232-1238 (2008)
© 2008 Society of Surgical Oncology
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Original Article

Messenger RNA Expression of Vascular Endothelial Growth Factor and Its Receptors in Primary Colorectal Cancer and Corresponding Liver Metastasis

Hirotoshi Kobayashi, MD, PhD1,2, Kenichi Sugihara, MD, PhD1, Hiroyuki Uetake, MD, PhD1, Tetsuro Higuchi, MD, PhD1, Masamichi Yasuno, MD, PhD1, Masayuki Enomoto, MD, PhD1, Hidekazu Kuramochi, MD2, Heinz-Josef Lenz, MD3, Kathleen D. Danenberg, BS4 and Peter V. Danenberg, PhD2

1 Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
2 Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, USA
3 Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, USA
4 Response Genetics, Inc, Los Angeles, USA

Correspondence: Address correspondence and reprint requests to: Hirotoshi Kobayashi, MD, PhD; E-mail: h-kobayashi.srg2{at}tmd.ac.jp

Background: Antiangiogenic therapies have been developed recently in combination with traditional chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to clarify the association between messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and its receptors (VEGFR) in primary colorectal cancer and those in corresponding liver metastasis.

Methods: Thirty-one paired formalin-fixed, paraffin-embedded tumor tissues of colorectal cancer and liver metastasis were dissected by laser capture microdissection. After the mRNA was isolated, a quantitative fluorescent dye real-time reverse transcription-polymerase chain reaction system was used for gene expression measurement.

Results: There was a positive correlation between VEGF mRNA levels in primary colorectal cancer and those in matched liver metastasis (P = .0083, rs = 0.48). However, there was no association between mRNA levels of VEGFRs in primary tumor and those in liver metastasis. The mRNA levels of VEGF were associated with those of VEGFR-1 (P = .0026, rs = 0.39) but not with those of VEGFR-2. The mRNA levels of VEGF were higher than that of either of the VEGFRs (P < .0001).

Conclusions: We can predict VEGF mRNA levels, but not those of VEGFRs, in liver metastasis by measuring those in primary colorectal cancer. The mRNA expression of VEGFRs may be more dependent on the surrounding environment than that of VEGF. These results should be useful for the formulation of antiangiogenic therapies for metastatic colorectal cancer. Further studies will be necessary to validate these preliminary data.

Key Words: VEGF • VEGF receptor • Colorectal cancer • Liver metastasis • RT-PCR






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