Abstracts / Lung Cancer 15 (1996) 259,279 261

AImlmT~HuMAN -URAL-OMA NUDE-MOUSEMODEL ph. AstouW, x. wat+. R.M. ~~ntan2.3, c Boutin 1. t Deparfmentof pneumology Hopital la Conception, Marseille. France. ZAntiCancer Inc., 7917 Ostmw Stmet, San Diego, CA 92 111, USA. 3 Laboratory of Cancer Biology, School ofMedicine. UCSD, LoJolla, CA 920934609 us4

Htmtan malignant pleural mesothelioma is an agressive cancer with no effective treatment A relevant animal model is needed for studying the biology and for discovery of effective treatment. To meet this need we have developed an orthotopic transplant model for malignant ____ ---.-..-...-...~ ~~~ ~~ with malignant mesothelioma werkimplanted on the parietal pleura of nude mice. All patient tumors gave rise to locally growing tumors in the mice. The transplanted mice presented symptoms of malignancy such as decrease in physical activity and signs of tumor-related respiratory distress. These animals were shown to have an extensive tumor spreading intheipsilat~~asUaswntralata;llpleural~vityasweUasmediastinal lymph node. When the lesions were still confined to the ipsilatcral parietal pleura, the implanted animals were in better physical condition. The macroscopic features usually found in the patients were also found in the implanted animals such as nodules, masses as well as pleural tllanes. Hktologic examimion revealed malignant mesothetiomasimilar to that from which the original tumor specimen was derived. Orthotopic parietal pleura implantation of fresh histololigical human malignant mesothelioma thus allows mesothelioma growth in an animal model that mimics the clinical spreading of the human disease. This model provides for the first time a useful human model for biological studies to this disease and for developing effective treatment.

TUMOUR~INM P Baas, JH Schouwink, CM Korse, JMG Bonfrer. The Netherlands Cancer Institute (Antoni van Leeuwenhoek Ziekenhuis, Plesmoniaon 121, 1066 CXAmsterdam, The Netherlands

The clinical mursc of mesotheliomas is often difftcult to predict, especially since measurable target lesions are not often available. The effect of, experimental, chemotherapeutic regimens is therefore not easily assessed since growth rate camrot be estimated properly. Ttmtour markers could well be of use as prognostic signs or as early signs of response. At time of diagnosis we measured CEA and CAI 25 as markers of possible involvement ofthe pleuraand TPA and Cytokemtin 19 (Cyfra 21. I) in the serum of 27 patients in the Netherlands Cancer Institute. Tumour staging was Budchart I (20 patients) Stage II to IV in 7 patients. The tumour markers could not differentiate between the various stages. Using the reference values as given by the manufacturers CA125 TPA and Cyfra 2 1.1 were elevated in 33%. 48% and 37%. respectively. Cyfra and TPA were highly correlated compared to CEA and CA125 in this disease. Univariate analysis showed a significant relation between survival and both cytokeratin markers. In 4 cases Cyfra was measured prospectively and appears to be useful as parameter for measuring response (progression).

D~PlXJRALFKDlKlXXlN~ CARCINOMA IN MAN - A STUDY USING A DUAGISOTOPE

Basrart G.S., Dev D., Joseph J., Smith MJ. Respiratoty Unit, Rotherham General Hospital. Rotherhom, S. Yorkshire. England

Pleuraletrusionresultsfromanimbalancebetweenthemteofformation and rate of removal of fluid from the pleural space. We have monitored the formation and drainage of pleural fluid in man using a radiolabelled

protein technique (Nucl Med Commun 1992, I3 :432). Fifty-two patien:s with free flowing pleural e&ion from a variety of causes were investigated using this method. Fluid formation was monitored by mesuring the rate

withIndium-l13m~n).FIuiddrainage[Kout]wasestimatedbymeasuring the rate of appearance in the blood of radio-labelled albumin (Iodine-125) injected directly into theeffusion. The Kin and Kout were calculated using a three compartmental model and expressed below as mean f se. m. (low).

Diagnosis n Kin Kout

Mesothelioma 10 9.9k3.2 4.7io.9

Lung Cancer 18 30.1 i 12.6 24.2i3.5

Met. Cancer 7 39.Ozt24.1 28.0i7.3

Cardiactihue 8 7.6* 1.9 35.1*9.9

Others 9 18.5i9.6 53.2ct9.7

Gutflow (Kout) was significantly lower in effusions due to mesothelioma compared to primary lung cancer @<0.005), metastatic lung cancer @<o.OOl) orcardiacfailure @<o.OOl). We speculate that in mesothelioma, the predominant mechanisms of effusion formation is the effect of the tumour on the lymphatic system, resulting in IowKout. even before the tumour produces the gross pleural encasement. In carcinomatous involvement ofthe pleural, however, the predominant mechanismappears to be a modest increase in rate of exudation due to increased vascular permeability. Because of the apparent difference in mechanism and consequently low values of Kout, the isotope technique could form the basis of a simple methodology for distinguishing malignant pleural etfusions associated with mesothelioma from those associated with carcinoma -a common clinical dilemma.

AMAD- AND HBME-I. EVALUATION OF THEIR IMMUNO- REAtzTllwmwrrHMAuGNANT-OMA Donna A., Bellingeri D., Pavesi M.*, PastormerloM.* andBetta I? G.* Service of Pathological Anatomy. Alessandria Hospital. Alessandrio. Italy. *Service of Pathological Anatomy. Santa Spirit0 Hospital. CasaIe Monferrato. Italy.

The rabbit polyclonal AMAD- (Byk Gulden, Italy) and the mouse monoclonal HBME-I (Dako, Italy) are the only two antibodies raised to mesothelioma-associated antigens and which have up to now been reported to show reactivity on par&in-embedded tissues. This study aims at comparing the efftcacy of the two antibodies in the immumhistochemical identilication of mesothelioma cells in pleural biopsy specimens. IXventy definite malignant mesothelioma (MM) (epithelial type : n=13 ; sarcomatoustype : n=5 ; mixedtype : n=2) were investigated using a streptavidin-biotin-peroxidase method. AMAD- reacted positively in 50% or more of tumour cells in all cases with a focal or dif8rse cytoplasmic pattern and a staining intensity ranging from weak to strong, as is already known (Cancer 63.133 1,1989). Conversely HBME-I showed consistent labelling of moderate to strong intensity in > 20% of tumour cells in 12/20 cases. The staining always appeared to be in the cell membraue in a thick pattern, but occasional cytoplasmic reactivity was seen. In particular, HBME-1 reactedpositivelywith IO/l3 epithelial-type MM, O/5 sarcomatous type MM and the epithelial component alone of the 2 mixed-type MM. Therefore, AMAD- proved a more sensitive mesothelioma marker than HBME-I. This finding supports the view that AMAD- is an antibody specific for the mesothelial lineage, since it recognises a growth factor for mesothelial cells (Expl Cell Biol57, 193, 1989). whereas HBME-I, in the light of both the absence of reactivity with sarmmatous MM and the acknowledged positive cytoplasmic