discrimination of human small cell and non-small cell lung tumors by a panel of monoclonal...

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81 as neuroblastoma. Among the normal cells, Kulchitski cells of lung, thyroid gland, adrenal gland, Langerhans islet, and nervous tissues were positive. Thus, the expression of NE-25 antigen is closely associated with the neural and/or (neuro)endocrine differentiation state. On the contrary, PE-35 antigen was present on four major types of lung car- cinomas as well as on squamous cell car- cinoma and adenocarcinomas of various tissues, but it was absent from nervous tissue tumors. Thus, PE-35 antibody showed a 'pan-epithelial' reactivity. Analysis by NE-25 and PE-35 antibodies provided evidence for the heterogeneities of SCLC by demonstrating four surface phenotypes, with the NE-25+/PE-35 + phenotype being most common. In addition, the results supported the current under- standing that various histological types of lung carcinoma, including SCLC, are derived from a stem cell of the bronchial epithelium. Discrimination of Human Small Cell and Non-Small Cell Lung Tumors by a Panel of Monoclonal Antibodies. Tong, A.W., Lee, J.C., Stone, M.J. Im- munology Research Unit, Charles A. Sam- mons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, U.S.A. J. Natl. Cancer Inst. 77: 1023-1033, 1986. The immunohistochemical reactivity of biopsy specimens from different human lung tumor cell types was examined with 4 human small cell lung carcinoma (SCLC)- reactive monoclonal antibodies (MoAbs) (SCLC 1096, SCLC 2051, SCLC 3121, and $CLC 5023) generated in this laboratory, with the use of Formalin-fixed, paraffin- embedded tissue sections. Each MoAb leacted preferentially with SCLC tumors (62-97% of 29 cases tested), with low-to- moderate cross-reactivity with non-SCLC tumors (SCLC 1096, 13.7%; SCLC 2051 and SCLC 3121, 9.8% each; SCLC 5023, 41% of 51 cases tested). None of the 4 MoAbs reacted with nonmalignant lung biopsy specimens. SCLC tumors were characterized by their collective immunoperoxidase reactivity with the MoAb panel of SCLC 2051, SCLC 3121, and SCLC 5023. Based on unequivocal positive reactions with at least 2 of the 3 MoAbs, this MoAb panel correctly identified 97% (28/29) of SCLC cases of 80 lung tumor cases tested. By contrast, only 4 of 51 (7.8%) non-SCLC cases were positive by the same criterion. These observations suggest that immunohistochemical analysis with these SCLC-reactive MoAbs could help in discriminating small cell from other human lung carcinoma cell types. On the Advent and Necessity of Molecular Biology in the Clinical Management of Lung Cancer. Rahbek-Sorensen, H., Olsson, L. Depart- ment of Thoracic Surgery, State Univer- sity Hospital, Rigshospitalet, DK-2100 Copenhagen, DenmarK. Thorac. Cardiovasc. Surg. 34: 345-350, 1986. The very rapidly expanding knowledge and technologies of molecular biology are reviewed with special reference to problems in the clinical management of lung cancer. Genetic events, tumor- associated antigens, production of murine and human monoclonal antibodies, culture of cell lines, intratumoral phenotypic diversity and squamous-lung-cancer- associated antigens are discussed and re- lated to possible therapeutical approaches. A monoclonal antibody with high specificity for squamous cell lung cancer reacted positively in blood samples and tissue extracts in about 80%. Its use as a marker during follow-up after surgical treatment is demonstrated by examples. It is concluded that there will be limiting factors in the therapeutic use of monoclonal antibodies, such as intratumoral phenotypic diversity. Genetic analysis might be a method for selecting a high risk group of individuals in whom exposure to car- cinogenic factors, such as cigarette smoking, would be fatal. Murine monoclonal antibodies can be used in vitro for screening, for histological ex- amination and for prognostic studies. Human monoclonal antibodies should be used for in vivo purposes as well as for the screening of primary tumor and metas- tases for the therapy. To achieve usable results, the monoclonal antibodies should be raised against the cell membranes that, in particular, are expressed on the stem cells of the neoplastic cell population. c-K-ras Codon 12 GGT-CGT Point Mutation: An Infrequent Event in Human Lung Cancer. Milici, A., Blick, M., Murphy, E., Gutterman, J.U. Department of Clinical Immunology, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, TX 77030, U.S.A. Biochem. Biophys. Res. Commun. 140: 699-705, 1986. Hu-c-ras represent a family of on- cogenes which are capable of inducing malignant transformation in the NIH/3T3 mouse cell line. Associated with this transformation are specific point muta- tions observed in the 12th and 61st codon of c-K-ras and N-ras and c-Ha-ras, respectively. These base changes generate, in some instances, a new restriction enzyme, cleavage site and a restriction fragment length polymorphism (RFLP). One such RFLP has recently been reported for the mutation GGT-CGT at codon 12 of c-K-ras. Our data suggest that this point mutation is rarely present in human lung cancer and there- fore is not likely to play a major role in cancer development.

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81

as neuroblastoma. Among the normal cells, Kulchitski cells of lung, thyroid gland, adrenal gland, Langerhans islet, and nervous tissues were positive. Thus, the expression of NE-25 antigen is closely associated with the neural and/or (neuro)endocrine differentiation state. On the contrary, PE-35 antigen was present on four major types of lung car- cinomas as well as on squamous cell car- cinoma and adenocarcinomas of various tissues, but it was absent from nervous tissue tumors. Thus, PE-35 antibody showed a 'pan-epithelial' reactivity. Analysis by NE-25 and PE-35 antibodies provided evidence for the heterogeneities of SCLC by demonstrating four surface phenotypes, with the NE-25+/PE-35 + phenotype being most common. In addition, the results supported the current under- standing that various histological types of lung carcinoma, including SCLC, are derived from a stem cell of the bronchial epithelium.

Discrimination of Human Small Cell and Non-Small Cell Lung Tumors by a Panel of Monoclonal Antibodies. Tong, A.W., Lee, J.C., Stone, M.J. Im- munology Research Unit, Charles A. Sam- mons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, U.S.A. J. Natl. Cancer Inst. 77: 1023-1033, 1986.

The immunohistochemical reactivity of biopsy specimens from different human lung tumor cell types was examined with 4 human small cell lung carcinoma (SCLC)- reactive monoclonal antibodies (MoAbs) (SCLC 1096, SCLC 2051, SCLC 3121, and $CLC 5023) generated in this laboratory, with the use of Formalin-fixed, paraffin- embedded tissue sections. Each MoAb leacted preferentially with SCLC tumors (62-97% of 29 cases tested), with low-to- moderate cross-reactivity with non-SCLC tumors (SCLC 1096, 13.7%; SCLC 2051 and SCLC 3121, 9.8% each; SCLC 5023, 41% of 51 cases tested). None of the 4 MoAbs reacted with nonmalignant lung biopsy specimens. SCLC tumors were characterized by their collective immunoperoxidase reactivity with the MoAb panel of SCLC 2051, SCLC 3121, and SCLC 5023. Based on unequivocal positive reactions with at least 2 of the 3 MoAbs, this MoAb panel correctly identified 97% (28/29) of SCLC cases of 80 lung tumor cases tested. By contrast, only 4 of 51 (7.8%) non-SCLC cases were positive by the same criterion. These observations suggest that immunohistochemical analysis with these SCLC-reactive MoAbs could help in discriminating small cell from other human lung carcinoma cell types.

On the Advent and Necessity of Molecular Biology in the Clinical Management of Lung Cancer.

Rahbek-Sorensen, H., Olsson, L. Depart- ment of Thoracic Surgery, State Univer- sity Hospital, Rigshospitalet, DK-2100 Copenhagen, DenmarK. Thorac. Cardiovasc. Surg. 34: 345-350, 1986.

The very rapidly expanding knowledge and technologies of molecular biology are reviewed with special reference to problems in the clinical management of lung cancer. Genetic events, tumor- associated antigens, production of murine and human monoclonal antibodies, culture of cell lines, intratumoral phenotypic diversity and squamous-lung-cancer- associated antigens are discussed and re- lated to possible therapeutical approaches. A monoclonal antibody with high specificity for squamous cell lung cancer reacted positively in blood samples and tissue extracts in about 80%. Its use as a marker during follow-up after surgical treatment is demonstrated by examples. It is concluded that there will be limiting factors in the therapeutic use of monoclonal antibodies, such as intratumoral phenotypic diversity. Genetic analysis might be a method for selecting a high risk group of individuals in whom exposure to car- cinogenic factors, such as cigarette smoking, would be fatal. Murine monoclonal antibodies can be used in vitro for screening, for histological ex- amination and for prognostic studies. Human monoclonal antibodies should be used for in vivo purposes as well as for the screening of primary tumor and metas- tases for the therapy. To achieve usable results, the monoclonal antibodies should be raised against the cell membranes that, in particular, are expressed on the stem cells of the neoplastic cell population.

c-K-ras Codon 12 GGT-CGT Point Mutation: An Infrequent Event in Human Lung Cancer. Milici, A., Blick, M., Murphy, E., Gutterman, J.U. Department of Clinical Immunology, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, TX 77030, U.S.A. Biochem. Biophys. Res. Commun. 140: 699-705, 1986.

Hu-c-ras represent a family of on- cogenes which are capable of inducing malignant transformation in the NIH/3T3 mouse cell line. Associated with this transformation are specific point muta- tions observed in the 12th and 61st codon of c-K-ras and N-ras and c-Ha-ras, respectively. These base changes generate, in some instances, a new restriction enzyme, cleavage site and a restriction fragment length polymorphism (RFLP). One such RFLP has recently been reported for the mutation GGT-CGT at codon 12 of c-K-ras. Our data suggest that this point mutation is rarely present in human lung cancer and there- fore is not likely to play a major role in cancer development.