HER-2/neu overexpression is rare in hepatocellular carcinoma and not predictive of anti-HER-2/neu regulation of cell growth and chemosensitivity.
BACKGROUND
The overexpression of HER-2/neu oncogene has been implicated in the development and modulation of many types of cancer. However, whether HER-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 10 microg/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.
Hsu
Chiun
C
Department of Oncology, National Taiwan University Hospital, Taipei.
Huang
Chin-Lun
CL
Hsu
Hey-Chi
HC
Lee
Po-Huang
PH
Wang
Shiou-Jeng
SJ
Cheng
Ann-Lii
AL
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab