Yano 18_7

A monoclonal antibody to HER2 protein is widely used in the treatment of patients with HER2-overexpressing breast cancer and has also been found to exhibit antitumor activity in human gastric cancer cells that overexpress HER2. The purpose of this study was to evaluate the frequency of HER2 overexpression and concordance between the results for protein expression and gene amplification in both surgical and biopsy specimens of gastric cancer as assessed with two commercial kits, one for immunohistochemistry (IHC) and the other for fluorescence in situ hybridization (FISH). The specimens consisted of formalin-fixed, paraffin-embedded sections of biopsy specimens and surgically resected tumors from 200 cases of invasive gastric cancer that had been treated surgically at the National Cancer Center Hospital East. The lesions were analyzed with the IHC kit, and expression was graded by the United States Food and Drug Administration (FDA)-approved grading system. Gene amplification was evaluated by FISH. IHC revealed HER2 overexpression in 46 of the 200 (23%) cases. The FISH assay was technically successful in 199 cases (99.5%), and gene amplification was observed in 54 cases (27.1%). The concordance rate between the results obtained by IHC and FISH was 86.9%. The concordance rate between the findings in the surgically resected tumors and the 200 pre-treatment biopsy specimens was 88.7%. HER2 expression can be assessed in gastric cancer with a commercial kit as previously reported in breast cancer. Even small biopsy specimens were found to be suitable for evaluating gastric cancer for HER2 overexpression. Introduction The HER2 (also called c-erbB2) is a proto-oncogene and is located on chromosome 17q21 (1). HER2 encodes a Mr 185,000 transmembrane glycoprotein, which is a member of the HER receptor family and possesses tyrosine kinase activity. Overexpression of HER2 protein has been described in approximately 25-30% of invasive breast cancers, and it has been used as a marker of resistance to various therapeutic modalities, and short disease-free survival (2,3). Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, CA), a monoclonal antibody to the HER2 protein, is a promising agent for the treatment of breast cancer patients with a poor prognosis, and Slamon et al have reported that addition of Trastuzumab to the chemotherapy regimen yields a significantly higher response and prolongs time to progression and overall survival of a breast cancer patients with HER2 overexpression (4). Various methods are available to determine the HER2 status of breast cancer, however, many of them require fresh tissue, involve a complicated procedure, and are costly. Immunohistochemistry (IHC) is widely used to evaluate protein expression in formalin-fixed, paraffin-embedded specimens, and, Southern blot hybridization is recognized as the standard method for analysis of HER2 gene amplification, but the procedure requires a large, fresh specimen (5). Fluorescence in situ hybridization (FISH) can be used to analyze small formalin-fixed, paraffin-embedded specimens for gene amplification, and Press et al have evaluated FISH as a mean of assessing HER2 amplification in breast cancer (3). In their study, FISH was used to test for HER2 amplification in 140 breast cancers in which gene amplification had already been demonstrated by Southern hybridization and it was found to have a sensitivity of 98% and a specificity of 100%. IHC and FISH are widely used methods for evaluating HER2 status for breast cancer, furthermore, Food and Drug Administration (FDA) in the United States approved IHC and FISH tests to determine HER2 status for breast cancer patients: Hercep test kit (DakoCytomation Denmark A/S, Glostrup, Denmark), and PathVysion HER2 DNA probe kit (Vysis Inc., Downers Grove, IL). Many investigators have ONCOLOGY REPORTS 15: 65-71, 2006 65 Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer TOMONORI YANO1,2, TOSHIHIKO DOI2, ATSUSHI OHTSU2, NARIKAZU BOKU2, KAORU HASHIZUME3, MAMORU NAKANISHI4 and ATSUSHI OCHIAI1 1Pathology Division, Reseach Center for Innovative Oncology; 2Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba; 3Medical Science Department, DakoCytomation Co. Ltd.; 4Bioscience Division, FALCO Biosystems Ltd., Kyoto, Japan Received July 18, 2005; Accepted September 16, 2005 _________________________________________ Correspondence to: Dr Atsushi Ochiai, Pathology Division, Reseach Center for Innovative Oncology, NCC-Kashiwa, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan E-mail: [email protected]