We conclude that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.
Immunohistochemical study may be used for detecting micrometastases by their expression of tumor-associated antigens. In 48 specimens of colorectal cancer from 47 patients, 49 of 249 lymph nodes (median, five per patient; range, 2-11) examined by light microscopic study contained tumor deposits. Sections of all lymph nodes were also examined by immunohistochemical study for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression using the indirect immunoperoxidase staining method. All 49 lymph node metastases (100%) from 20 patients stained positively for CEA and 45 (92%) expressed EMA. Of the 200 lymph nodes without metastases on light microscopic examination, anti-CEA revealed a single micrometastasis in a patient staged as Dukes' B. No additional metastases were detected with anti-EMA. In this series of patients immunohistochemical study has, therefore, influenced the histologic staging in only one patient (2%) and thus does not offer a significant benefit over conventional histologic staging.
With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 IgG2a and I IgA) have been prepared against the external domain of the product of the c-erbB-2 proto-oncogene. All 4 antibodies stain frozen sections of tissues that over-express the product of the c-erbB-2 proto-oncogene, and competitive binding assays showed that the antibodies recognized 2 non-overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190 kDa protein from 35S-methionine-labelled breast carcinoma cells where the c-erbB-2 is amplified (BT 474 and MDA-MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR12 stains formolsaline-fixed sections of breast carcinoma tissue that over-expresses the product of the c-erbB-2 proto-oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio-immunoscintigraphic and therapeutic applications.
Treatment of rats with 25 mg/kg/day of cyclosporin A suppressed their immune response to skin allografts. Withdrawal of cyclosporin A treatment led to complete recovery of specific immune responsiveness and the time taken for recovery was independent of the duration of treatment. Titration of the dose of cyclosporin A administered in vivo indicated that doses of 12 mg/kg/day or less were not fully immunosuppressive.
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