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NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, and Naval Hospital, Bethesda, Maryland 20814
Using immunohistochemistry, radiobinding, and indirect immunofluorescence assays, seven distinct cell surface antigens, detected by monoclonal antibodies, were analyzed for the degree of homogeneity or heterogeneity of antigen expression on a panel of human small cell lung cancers. The panel included 7 tumors taken directly from patients, 21 established cell lines (9 of which were derived from different metastatic sites of 3 patients), and 33 clonal derivatives of 3 lines. With all assays, considerable heterogeneity of antigen expression between tumors from different patients was observed. In both fresh tumors and in cell lines, as well as in cell lines established from different metastatic sites in an individual patient, we observed intratumor heterogeneity finding antigen positive and negative cells and variation in antigenic density, by immunohistochemistry and indirect immunofluorescence assays. Antigenic expression was not cell cycle dependent. In addition, when cell lines or patient samples expressing antigen positive and antigen negative tumor cells were cloned, heterogeneity of antigenic expression was still present in the clonal lines. This suggests that either the expression of the antigen was not heritable and/or the ability to regenerate antigenic heterogeneity is an intrinsic property of the tumor cells. The heterogeneity of antigen expression on lung cancer cells has significant implications for the use of these and other monoclonal antibodies in the study and therapy of lung cancer.
1 The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense.
2 Current address: Clinica Medica III, University of Milan, Via Pace 15, Milan, Italy.
3 To whom requests for reprints should be addressed, at NCI-Navy Medical Oncology, Building 8, Room 5101, Naval Hospital, Bethesda, MD 20814.
Received 2/ 3/84. Revised 12/ 6/85. Accepted 1/ 4/86.
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