[A further study on the relationship between the HLA and longevity or aging].
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Biomedical subjects
Publications and source records attributed to Y X Ma.
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We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.
Bronchopulmonary carcinomas were analyzed immunohistochemically using monoclonal antibody 624A12. The antibody was raised against a human "small cell carcinoma" cell line NCI-H69. It recognizes a particular sugar sequence in lacto-N-fucopentose III, which is preserved in formalin fixed and paraffin embedded tissue. Various bronchopulmonary carcinomas revealed characteristic patterns of immunoreactivity. Forty nine/50 adenocarcinomas were immunoreactive either diffusely or focally. The immunostaining was usually limited to the cell membranes with occasional intracytoplasmic immunostaining in large cells. The only negative case had been irradiated before surgical resection. Twenty seven/38 squamous cells carcinomas did not immunostain while the remaining 11 displayed focal immunoreactivity in areas of "loose cellular apposition" associated with necrosis and, rarely, in squamous pearls. All of six adenosquamous carcinomas showed immunoreactivity focally. Eleven/30 large cell carcinomas and 10/11 bronchiolo-alveolar carcinomas were either diffusely or focally immunoreactive. Seven/26 intermediate cell neuroendocrine carcinomas were focally immunoreactive while none of 33 typical small cell neuroendocrine carcinomas, 21 carcinoids, and 10 well differentiated neuroendocrine carcinomas was immunoreactive. An adenoid cystic carcinoma was diffusely immunoreactive, and a mucoepidermoid carcinoma was focally immunoreactive. We conclude that various bronchopulmonary neoplasms have characteristic patterns of distribution of this antigen, and that monoclonal antibody 624A12 may be useful for the differential diagnose among bronchopulmonary carcinomas, and their differential diagnosis from pleural mesotheliomas.
Forty-three malignant pleural mesotheliomas and 10 known metastatic pulmonary adenocarcinomas to the pleura were studied by immunohistochemistry using monoclonal antibodies 44-3A6 and 624A12. Monoclonal antibodies 44-3A6 and 624A12 were raised against human pulmonary carcinoma cell lines; they recognize a membrane-associated protein of 40,000 mol wt and a specific sugar sequence of lacto-N-fucopentose III, respectively. Samples were also studied with a broad-spectrum antikeratin antibody and a polyclonal antibody to carcinoembryonic antigen (CEA). These investigations were performed on formalin-fixed and paraffin-embedded tissues. The mesotheliomas comprised only grossly evident, pleurectomized, or pneumonectomized cases; they included 22 epithelial, 15 biphasic, and 6 spindle cell types. Electron-microscopic study was also done on 9 cases. None of the mesotheliomas was immunoreactive to 624A12, while 9/10 metastatic pulmonary adenocarcinomas were convincingly immunoreactive. Monoclonal antibody 44-3A6 immunostained all of the metastatic adenocarcinomas strongly, whereas only 10/43 mesotheliomas were focally and weakly immunoreactive. The latter included 5 epithelial and 4 biophasic mesotheliomas and 1 spindle cell mesotheliomas; the immunoreaction was confined to scattered single cells, and the staining pattern was readily discernible from that of adenocarcinomas. Forty of 43 mesotheliomas were strongly immunoreactive with the broad-spectrum anti-keratin antibody, whereas 8/10 metastatic pulmonary adenocarcinomas showed focal and rather weak staining. Seven of 10 metastatic adenocarcinomas were immunoreactive to anti-CEA antibody, while only 15/43 mesotheliomas displayed weak immunoreactivity. It is concluded that monoclonal antibodies 44-3A6 and 624A12 are excellent phenotypic markers of metastatic pulmonary adenocarcinomas to the pleura and thus are useful for the differential diagnosis of pleural mesotheliomas. Given conventionally fixed and processed tissues, it appears that the combined use of these monoclonal antibodies may be more effective for that differential diagnosis than anti-CEA and anti-keratin antibodies.
This paper describes an immunoglobulin G1 mouse monoclonal antibody (MCA) 44-3A6 directed against a human adenocarcinoma of the lung, cell line A549. This hybrid is a fusion product of the mouse myeloma SP 2/0.Ag14 and spleen cells from a BALB/c mouse which had been hyperimmunized with A549. Live cell radioimmunoassays, immunofluorescences, and fluorescent activated cell sorter analysis indicate that MCA 44-3A6 reacts with a cell surface antigen. Western blot analysis identifies a major antigen band with the apparent molecular weight of 40,000. Enzyme treatment of A549 target plates shows that the antigen is sensitive to proteases. This MCA does not react with carcinoembryonic antigen. Patients having a variety of different lung carcinomas do not appear to have detectable antigen in their serum, nor does the antigen appear to be shed into culture supernatants by human lung carcinoma cell lines. The antigen is preserved in formalin-fixed, paraffin-embedded tissue sections and shows a cell surface and/or cytoplasmic staining pattern. Immunohistochemical staining of various bronchopulmonary carcinomas demonstrated binding to be restricted to tumors with features of "glandular" differentiation. This MCA may have clinical and diagnostic utility due to its selective binding for a subset of carcinomas of the lung.
A monoclonal antibody, 44-3A6, was raised against the human pulmonary adenocarcinoma cell line A549. This antibody recognizes a protein antigen at the cell surface, which is preserved after formalin fixation and paraffin embedding. Immunohistochemical staining of lung tissue with this antibody revealed diffuse immunoreactivity of type II pneumocytes. Bronchial epithelial cells were also focally immunoreactive. Immunostaining of various bronchopulmonary carcinomas demonstrated characteristic patterns of reactivity. All of the 42 adenocarcinomas and 18 carcinoids were strongly immunoreactive either diffusely or focally. The immunoreaction occurred at the cell membrane and/or in the cytoplasm. None of the 39 squamous cell carcinomas, 12 bronchioloalveolar carcinomas, and 30 small cell neuroendocrine carcinomas was immunostained. Ten intermediate cell neuroendocrine carcinomas and 8 well-differentiated neuroendocrine carcinomas were relatively weakly immunoreactive, while 7 and 2 of them were negative. Six adenosquamous carcinomas were focally positive in glandular and "basaloid" areas, whereas squamous areas were negative. Twenty-one large cell carcinomas were focally immunoreactive, while 6 were negative. It appears that MCA 44-3A6 is an effective marker for certain features of "glandular" differentiation, which may be present even in tumors lacking obvious glands, and that it may be useful for the differential diagnosis of various bronchopulmonary carcinomas.
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