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Vascular Endothelial Growth Factor Messenger RNA Expression Level Is Preserved in Liver Metastases Compared with Corresponding Primary Colorectal Cancer

Authors' Affiliations: ¹ University of Southern California/Norris Comprehensive Cancer Center; ² Response Genetics, Inc., Los Angeles, California; and ³ Department of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan

Requests for reprints: Peter V. Danenberg, University of Southern California/Norris Comprehensive Cancer Center, NOR 5318, 1441 East Lake Avenue, Los Angeles, CA 90033. Phone: 323-865-0517; Fax: 323-865-0105/323-224-3096; E-mail: pdanenbe{at}usc.edu.

Purpose: Increased vascular endothelial growth factor (VEGF) expression is associated with colorectal cancer liver metastases. It is reasonable to expect that measurement of VEGF in liver metastases would provide the best prediction of therapy benefit for VEGF-targeted drugs, such as bevacizumab (Avastin). In this study, we evaluated how VEGF mRNA level in primary colorectal cancer was related to that in corresponding liver metastases. Thirty-one pairs of primary colorectal cancer and corresponding liver metastases were analyzed.

Experimental Design: Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse transcription. Quantitation of VEGF and internal reference gene (ß-actin) was done using real-time PCR (Taqman PCR).

Results: There was no difference between median VEGF mRNA levels of primary colorectal cancer and liver metastases (median value 3.79 versus 3.97: P = 0.989). On an individual basis, there was a significant correlation in VEGF mRNA expression between primary colorectal cancer and corresponding liver metastases (r_s = 0.6627, P < 0.0001). In addition, the VEGF mRNA levels of the patients who had two or more liver metastatic tumors were significantly higher than those of the patient who had solitary liver metastatic tumor in both primary cancer (5.02 versus 3.34: P = 0.0483) and liver metastases (4.38 versus 3.25: P = 0.0358).

Conclusion: Good prediction of VEGF mRNA levels in liver metastases can be obtained by measuring those of primary colorectal cancer. The risk of multiple liver metastatic tumors might be predictable by measuring VEGF mRNA expression in primary colorectal cancer. Further study is required to confirm these preliminary results.

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