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Submesothelial sarcoma: A subtype distinct from diffuse malignant and localized benign mesotheliomas
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A MURINE MODEL OF MESOTHELIOMA. Davis M., Manning L.S., Whitaker D., Mutsaers University Department of S.E., Robinson B.W.S. Medicine, Queen Elizabeth II Medical Centre, Nedlands, W. Australia 6009. Malignant mesothelioma is an aggressive tumour of the mesothelium. Study of this tumour has been hampered by the limited number of available patients in any particular institution. Therefore, there is a need for the establishment of animal models and representative cell lines to study the basic biology of this disease. In this study, 20 BALB/c and 20 CBA female mice were injection of 2.5mg of given an intraperitoneal Five to 27 months after crocidolite asbestos. exposure, 14 of the 40 mice injected were identified as having mesothelioma (5 BALB/c, 9 CBA) by established
Submesothelial sarcoma: A subtype distinct from diffuse malignant and localized benign mesotheliomas. M. Sumitomo, T. Uyama, K. Takahashi, K. Kondo, Y. Monden, and M. Tsuyuquchi The 2nd Dept. of Surq., School of Medicine, The University of Tokushima, Tokushima, Japan Mesotheliomas are classified as diffuse or localized. Although most localized mesotheliomas are benign, some show malignant features including invasion. We reviewed fourteen cases of mesotheliomas to clarify the relation between clinical and pathological features. Five were diaqnosed as diffuse, three as localized maliqnant, and six as localized benign. All diffuse and one localized malignant ones showed aggressive invasion and epithelial features even in fibrous components. Two localized malignant and all localized benign ones were located subpleurally. The former showed invasion and were sarcomatous. The latter were fibrous and entirely bland. These fibrous tumors lacked epithelial natures both immunohistochemically and ultrastructurally. Patients with diffuse or localized epithelial mesothelioma died within a year, but patients with localized fibrous one were free of disease more than 2 years after the surgery. These results indicate that localized malignant mesotheliomas devoid of epithelial features (submesothelial sarcomas) should be discriminated from the other subtypes.
cytological and histologicalparameters. Of these tumourswe have established12 as continuous cell lines Using with doubling times ranging from 16-60 hours. cytologicaland histologicalprocedures,and electron microscopy, these cell lines were confirmed as malignant mesothelioma. All lines were found to produce subcutaneous and intraperitonealtumours, however,only 2 did so in a consistentand predictable manner. This panel of murine mesotheliomasprovidesa representative tumourmodel for investigating potential diagnostic and therapeutic protocols and for the investigation of variousaspectsof the basic biology, immunologyand geneticsof mesothelioma.
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Distributionof the productsof variousoncogen in the tissue of malignantmesotheliomas Takumi Kishimoto(Kure Kyosai Hospital,Japan) The mutation of genes has been reported to In this study, be induced by asbestos exposure. the distribution of the various oncogenes in the induced tumor tissue of malignant mesothelioma by the asbestos exposure was examined by the "se against various antibody the of monoclonal oncogenes. [Material and Method] The tumor tissue of 11 cases with malignant mesothelioma were used in this study. All cases had occupational histories of asbestos exposure and significantly high number of asbestos bodies in the autopsied lung tissue. Histologically, 5 cases are biphasic type, 3 cases are epithelioidal and other 3 cases sarcomatous type. K-ras, H-ras, Pan-ras, C-abl, C-myc, N-myc, C-neu, c-fos, erb-B were used and the distribution of
the products of oncogenes were stained by AvidinBiotin complex (ABC) method. [Result] K-ras, H-r-as and erb-B were negative for these 11 cases and C-abl was positive only 1 case. C-myc and N-myc were detected in almost all epithelioidal type and the epithelial potion of mix type. C-neu, C-fos and Pan-x-as were positive for all type. C-neu was especially high positivity for various type of malignant tumor. [Conclusion] These findings may suggest that the mutation of oncogenes may play some parts of the carcinogenicity of malignant mesothelioma induced by asbestos exposure.
Mucicarmine. PAS-Diastase and CEA-Positive nrEglthelial 'Mesptheliomas. P. Hammar,i?iagnostic S ecialties Laboratory B~r%?tf"~'W~shi"~n "lh:ostochemistry, a 0 0 is s ro ineYSA y use immunohistochemistry and electron microscopy to differentiate epithelial mesotheliomas from pulmonary Epithelial mesotheliomas are usually adenocarcinomas. mucicarmine, PAS-diastase and CEA negative, whereas about 60-75% of pulmonary adenocarcinomas are mucicarmine and PAS-diastase positive, and up to 90% are decorated by polyclonal CEA. During our pathologic evaluation of pleural neoplasms, we identified 10 epithelial mesotheliomas that were mucicarmine and/or PAS-diastase positive (diagnosis of mesothelioma confirmed by ultrastructural examination), with four of these mesotheliomas focally expressing CEA. The mucicarmine, PAS-diastase and CEA staining were eradicated or markedly reduced by pretreatment of the tissue sections with hyaluronidase, suggesting that hyaluronic acid was responsible for the positive In contrast, the staining reaction of 10 reactions. mucicarmine, PAS-diastase and CEA-positive pulmonary adenocarcinomas was not affected by hyaluronidase pretreatment of the tissue. Besides the usual ultrastructural features of epithelial mesotheliomas, the mucicarmine-positive mesotheliomas showed a medium-electron-dense secretory material covering the microvilli, which often crystallized, producing an ultrastructural morphology that we have observed only in mesotheliomas.
623
A MURINE MODEL OF MESOTHELIOMA. Davis M., Manning L.S., Whitaker D., Mutsaers University Department of S.E., Robinson B.W.S. Medicine, Queen Elizabeth II Medical Centre, Nedlands, W. Australia 6009. Malignant mesothelioma is an aggressive tumour of the mesothelium. Study of this tumour has been hampered by the limited number of available patients in any particular institution. Therefore, there is a need for the establishment of animal models and representative cell lines to study the basic biology of this disease. In this study, 20 BALB/c and 20 CBA female mice were injection of 2.5mg of given an intraperitoneal Five to 27 months after crocidolite asbestos. exposure, 14 of the 40 mice injected were identified as having mesothelioma (5 BALB/c, 9 CBA) by established
Submesothelial sarcoma: A subtype distinct from diffuse malignant and localized benign mesotheliomas. M. Sumitomo, T. Uyama, K. Takahashi, K. Kondo, Y. Monden, and M. Tsuyuquchi The 2nd Dept. of Surq., School of Medicine, The University of Tokushima, Tokushima, Japan Mesotheliomas are classified as diffuse or localized. Although most localized mesotheliomas are benign, some show malignant features including invasion. We reviewed fourteen cases of mesotheliomas to clarify the relation between clinical and pathological features. Five were diaqnosed as diffuse, three as localized maliqnant, and six as localized benign. All diffuse and one localized malignant ones showed aggressive invasion and epithelial features even in fibrous components. Two localized malignant and all localized benign ones were located subpleurally. The former showed invasion and were sarcomatous. The latter were fibrous and entirely bland. These fibrous tumors lacked epithelial natures both immunohistochemically and ultrastructurally. Patients with diffuse or localized epithelial mesothelioma died within a year, but patients with localized fibrous one were free of disease more than 2 years after the surgery. These results indicate that localized malignant mesotheliomas devoid of epithelial features (submesothelial sarcomas) should be discriminated from the other subtypes.
cytological and histologicalparameters. Of these tumourswe have established12 as continuous cell lines Using with doubling times ranging from 16-60 hours. cytologicaland histologicalprocedures,and electron microscopy, these cell lines were confirmed as malignant mesothelioma. All lines were found to produce subcutaneous and intraperitonealtumours, however,only 2 did so in a consistentand predictable manner. This panel of murine mesotheliomasprovidesa representative tumourmodel for investigating potential diagnostic and therapeutic protocols and for the investigation of variousaspectsof the basic biology, immunologyand geneticsof mesothelioma.
625
624
Distributionof the productsof variousoncogen in the tissue of malignantmesotheliomas Takumi Kishimoto(Kure Kyosai Hospital,Japan) The mutation of genes has been reported to In this study, be induced by asbestos exposure. the distribution of the various oncogenes in the induced tumor tissue of malignant mesothelioma by the asbestos exposure was examined by the "se against various antibody the of monoclonal oncogenes. [Material and Method] The tumor tissue of 11 cases with malignant mesothelioma were used in this study. All cases had occupational histories of asbestos exposure and significantly high number of asbestos bodies in the autopsied lung tissue. Histologically, 5 cases are biphasic type, 3 cases are epithelioidal and other 3 cases sarcomatous type. K-ras, H-ras, Pan-ras, C-abl, C-myc, N-myc, C-neu, c-fos, erb-B were used and the distribution of
the products of oncogenes were stained by AvidinBiotin complex (ABC) method. [Result] K-ras, H-r-as and erb-B were negative for these 11 cases and C-abl was positive only 1 case. C-myc and N-myc were detected in almost all epithelioidal type and the epithelial potion of mix type. C-neu, C-fos and Pan-x-as were positive for all type. C-neu was especially high positivity for various type of malignant tumor. [Conclusion] These findings may suggest that the mutation of oncogenes may play some parts of the carcinogenicity of malignant mesothelioma induced by asbestos exposure.
Mucicarmine. PAS-Diastase and CEA-Positive nrEglthelial 'Mesptheliomas. P. Hammar,i?iagnostic S ecialties Laboratory B~r%?tf"~'W~shi"~n "lh:ostochemistry, a 0 0 is s ro ineYSA y use immunohistochemistry and electron microscopy to differentiate epithelial mesotheliomas from pulmonary Epithelial mesotheliomas are usually adenocarcinomas. mucicarmine, PAS-diastase and CEA negative, whereas about 60-75% of pulmonary adenocarcinomas are mucicarmine and PAS-diastase positive, and up to 90% are decorated by polyclonal CEA. During our pathologic evaluation of pleural neoplasms, we identified 10 epithelial mesotheliomas that were mucicarmine and/or PAS-diastase positive (diagnosis of mesothelioma confirmed by ultrastructural examination), with four of these mesotheliomas focally expressing CEA. The mucicarmine, PAS-diastase and CEA staining were eradicated or markedly reduced by pretreatment of the tissue sections with hyaluronidase, suggesting that hyaluronic acid was responsible for the positive In contrast, the staining reaction of 10 reactions. mucicarmine, PAS-diastase and CEA-positive pulmonary adenocarcinomas was not affected by hyaluronidase pretreatment of the tissue. Besides the usual ultrastructural features of epithelial mesotheliomas, the mucicarmine-positive mesotheliomas showed a medium-electron-dense secretory material covering the microvilli, which often crystallized, producing an ultrastructural morphology that we have observed only in mesotheliomas.