HER-2/neu overexpression is rare in hepatocellular carcinoma and not predictive of anti-HER-2/neu regulation of cell growth and chemosensitivity
Journal
Cancer
Journal Volume
94
Journal Issue
2
Pages
415-420
Date Issued
2002
Author(s)
Abstract
BACKGROUND. The overexpression of HER-2/neu oncogene has been implicated in the development and modulation of many types of cancer. However, whether HEIR-2/neu overexpression plays a similar role in hepatocellular carcinoma (HCC) has not been determined. METHODS. Tissue specimens from 36 HCC patients who had been enrolled in 3 separate prospective clinical trials of systemic chemotherapy were studied by immunohistochemical staining. A polyclonal antibody (A0485; DAKO, Copenhagen, Denmark) against HER-2/neu and a horseradish peroxidase-based visualization system (Envision+, DAKO) was used. Scoring criteria was in accordance with the manufacturer's guidelines. Twelve HCC cell lines were examined for HER-2/neu overexpression by Western blotting. Single-agent growth regulatory activity of the anti-HER-2/neu antibody, trastuzumab (Herceptin; Genentech, South San Francisco, CA), and its combinative cytotoxicity with chemotherapeutic agents (doxorubicin, gemcitabine, cisplatin, irinotecan) were determined by a tetrazolium-based colorimetric assay (MTT test). RESULTS. All but one of the HCC tumor tissues were negative for HER-2/neu expression. The only patient with positive HER-2/neu expression was a 57-year-old male patient who achieved stabilization of disease for 2 months after chemotherapy. Eight of the 35 patients with negative HER-2/neu expression had had partial remission after chemotherapy (P = 0.78). Only one (Tong cells) of the 12 HCC cell lines had a significant level of HER-2/neu expression. However, trastuzumab up to 10μg/mL had no discernible growth inhibitory or chemosensitizing effect on Tong cells or any other cell lines. CONCLUSIONS. HER-2/neu overexpression is rare in human HCC tissues, and anti-HER-2/neu regulation appears to play little role in the treatment of this tumor. ? 2002 American Cancer Society.
SDGs
Other Subjects
cisplatin; doxorubicin; epidermal growth factor receptor; etoposide; gemcitabine; horseradish peroxidase; irinotecan; polyclonal antibody; polyclonal antibody A0485; recombinant alpha2a interferon; tamoxifen; tetrazolium; trastuzumab; unclassified drug; adult; article; assay; cancer regression; cancer resistance; carcinogenesis; cell growth; chemosensitivity; clinical article; colorimetry; controlled study; drug activity; drug cytotoxicity; female; gene overexpression; human; human cell; human tissue; immunohistochemistry; in vitro study; liver cell carcinoma; male; oncogene neu; prediction; priority journal; scoring system; Western blotting; Antibodies, Monoclonal; Antineoplastic Agents; Blotting, Western; Carcinoma, Hepatocellular; Cell Division; Drug Resistance, Neoplasm; Humans; Immunoenzyme Techniques; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Receptor, erbB-2; Tumor Cells, Cultured
Type
journal article