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A MURINE MODEL OF MESOTHELIOMA. Davis M., Manning L.S., Whitaker D., Mutsaers

S.E., Robinson B.W.S. University Department of 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 given an intraperitoneal injection of 2.5mg of crocidolite asbestos. Five to 27 months after exposure, 14 of the 40 mice injected were identified as having mesothelioma (5 BALB/c, 9 CBA) by established cytological and histological parameters. Of these tumours we have established 12 as continuous cell lines with doubling times ranging from 16-60 hours. Using cytological and histological procedures, and electron microscopy, these cell lines were confirmed as malignant mesothelioma. All lines were found to produce subcutaneous and intraperitoneal tumours, however, only 2 did so in a consistent and predictable manner. This panel of murine mesotheliomas provides a representative tumour model for investigating potential diagnostic and therapeutic protocols and for the investigation of various aspects of the basic biology, immunology and genetics of mesothelioma.

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Distribution of the products of various oncogen in the tissue of malignant mesotheliomas

Takumi Kishimoto (Kure Kyosai Hospital, Japan) The mutation of genes has been reported to

be induced by asbestos exposure. In this study, the distribution of the various oncogenes in the tumor tissue of malignant mesothelioma induced by the asbestos exposure was examined by the "se of monoclonal antibody against the various 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. Histo- logically, 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 Avidin- Biotin 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.

Submesothelial sarcoma: A subtype dis- tinct from diffuse malignant and local- ized 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 me- sotheliomas are benign, some show malignant features including invasion.

We reviewed fourteen cases of mesotheli- omas to clarify the relation between clinical and pathological features. Five were diaq- nosed as diffuse, three as localized maliq- nant, and six as localized benign. All dif- fuse 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 inva- sion and were sarcomatous. The latter were fibrous and entirely bland. These fibrous tumors lacked epithelial natures both immuno- histochemically and ultrastructurally. Pa- tients 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.

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Mucicarmine. PAS-Diastase and CEA-Positive nrEglthelial 'Mesptheliomas.

P. Hammar,i?iagnostic S ecialties Laboratory B~r%?tf"~'W~shi"~n YSA "lh:ostochemistry, a 0 0 is s ro ine y use

immunohistochemistry and electron microscopy to differentiate epithelial mesotheliomas from pulmonary adenocarcinomas. Epithelial mesotheliomas are usually 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 reactions. In contrast, the staining reaction of 10 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.