Introduction One of the most promising targets is the epidermal growth factor receptor (EGFR), a member of the type I receptor tyro- sine kinase (TK) family. Epidermal growth factor receptor is a 170-kDa transmembrane receptor that plays an important role in the differentiation and proliferation of epithelial cells. 1 Epidermal growth factor receptor is overexpressed in different solid cancer types, including up to 77% of colorectal cancers (CRCs) and is involved in malignant transformation and tumor growth through the interference of apoptosis, cellular prolifera- tion, angiogenesis, and metastasis. 2-6 Overexpression of EGFR has been associated with poor prognosis, 7,8 increased meta- static potential, 9 and has been suggested as a potential target for antitumor agents. 6,10-12 Studies have shown that monoclonal antibodies directed at EGFR inhibit the growth of EGFR- expressing cancer cells. 6 Epidermal Growth Factor Receptor and Epidermal Growth Factor Receptor Variant III Gene Expression in Metastatic Colorectal Cancer Abstract Submitted: Aug 9, 2006; Revised: Sep 5, 2006; Accepted: Sep 8, 2006 Address for correspondence: Heinz-Josef Lenz, MD, GI Oncology/ Colorectal Center, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Ave, Suite 3456, Los Angeles, CA 90033 Fax: 323-865-0061; e-mail: lenz@usc.edu 1 Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles 2 Response Genetics, Inc, Los Angeles, CA 3 Department of Preventive Medicine, University of Southern California/ Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles 4 Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan 5 Department of Molecular Biology and Biochemistry, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles Mizutomo Azuma, 1,4 Kathleen D. Danenberg, 2 Syma Iqbal, 1 Anthony El-Khoueiry, 1 Wu Zhang, 1 Dongyun Yang, 3 Wasaburo Koizumi, 4 Katsunori Saigenji, 4 Peter V. Danenberg, 5 Heinz-Josef Lenz 1 Purpose: The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR, or 6 EGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Because EGFRvIII has been reported to be tumor specific and has oncogenic potential, it is being investigated as a potential therapeutic target, but to our knowledge, there is only 1 previous report about EGFRvIII by immunohistochemistry in colorectal cancer. Our aim was to indicate the frequency of gene expressions of EGFRvIII and EGFR in metastatic colorectal cancer (mCRC). Patients and Methods: Forty-five patients with mCRC who received the chemotherapy for metastatic disease were analyzed for the EGFRvIII variant. Paraffin-embedded tumor tissues were dissected using laser-captured microdissection and analyzed for the EGFR and EGFRvIII messenger RNA expression using a quantita- tive real-time reverse-transcriptase polymerase chain reaction method. Gene expression values (relative messenger RNA levels) are expressed as ratios (differences from the cycle threshold values) between the target gene and internal reference gene (`-actin). Twenty-five women and 20 men with a median age of 55 years (range, 25-76 years) were included in this study. Results: We did not find any expression of EGFRvIII in these 45 patients except for control cell lines as U87.EGFRvIII. However, EGFR gene expression was found in 43 of 45 (95.6%) with a range of 0.38-2.83. Conclusion: Our results demonstrate that the expression of EGFRvIII is rare, but most colon cancer demonstrates EGFR gene expression. We conclude that EGFRvIII does not play an important role in mCRC. Clinical Colorectal Cancer, Vol. 6, No. 3, 214-218, 2006 Key words: Complementary DNA, Microdissection, Real-time polymerase chain reaction, RNA isolation Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1533-0028, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400. Contribution Original 214 • Clinical Colorectal Cancer September 2006