A b s t r a c t s 247

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IN SITU HYBRIDIZATION WITH A CHROMOSOME 1 SPECIFIC DNA PROBE ON INTERPHASE NUCLEI FROM PROSTATE CANCER CELLS. Josee J.K0nig, Sandra de Jong, Anne Hagemeijer*, Hans Romijn and Fritz H.SchrOder. Depts. of Urology and Genetics*, Erasmus University Rotterdam, The Netherlands.

With flow cytometry half of the prostate cancers show, apart from diploid cells, considerable populations of tetraploid and/or aneuploid cells. With collagenase treatment -which is a widely used method to obtain cell suspensions from solid tumors- nearly half of the nondiploid cells is destroyed, as was shown by us earlier. When the karyotype of these same tumors was investigated, nearly all tumors were seemingly diploid with occasional nonclonal aberrations. We used detection of numerical aberrations of chromosome 1 in interphase nuclei by in situ hybridization (ISH) with the SAT III probe PUC 1.77 for further investigation of this problem. ISH was performed on nuclei obtained before and after collagenase treatment and after tissue culture and the results were compared. ISH and FCM results were congruent in showing a decline of nondiploid cells after collagenase treatment. Two tumors showed high percentages of nondiploid cells ( 23% and 59% ) in fresh preparations which had declined to 12% and 9% respectively after tissue culture. Moreover, in both tumors all metaphases seemed normal diploid. We think this result is a clear indication that selection in favor of normal diploid cells can occur in short term tissue culture of prostate epithelium. More tumors need however be investigated in this way to draw a definite conclusion. This study was supported by a grant of the Netherlands Cancer Foundation.

60 COMBINED CYTOGENETIC AND IMMUNCYTOCHEMICAL STUDY ON PROSTATE CANCER

B Wullich I, T Lindenmeir {, G. Seitz 2, Th. Zwergel 3, G Unteregger I qnst. f~r Humangenetik. Univ. des Saarlandes. D-6650 H0mburg Saar 2Ins t . f i i r P a t h o l o g i e , U n i v . d e s S a a r l a n d e s , D - 6 6 5 0 H o m b u r g / S a a r a l r r o l o g i s c h e K l i n i k , U n i v . d e s S a a r l a n d e s , D - 6 6 5 0 H o m b u r g / S a a r

S p e c i f i c c h r o m o s o m a l c h a n g e s h a v e b e e n d i s c o v e r e d in s e v e r a l h u m a n so l i d r u m o r s a n d h a v e b e e n f o u n d to be u s e f u l t o o l s in t h e d i a g n o s i s , p r o g n o s i s , a n d c l a s s i f i c a t i o n o f t h e s e d i s e a s e s . H o w e v e r , o n l y f ew c y t o g e n e t i c d a t a a r e a v a i l a b l e on p r o s t a t i c c a n c e r , a n d s p e c i f i c c h r o m o s o m a l c h a n g e s a s s o c i a t e d w i t h t h i s k i n d o f t u m o r h a v e y e t b e e n f o u n d . We s t a r t e d to p e r f o r m c y t o g e n e t i c a n a l y s e s on ce l l c u l t u r e s o f p r i m a r y p r o s t a t i c a d e n o c a r c i n o m a s a n d m e t a s t a t i c l e s i o n s , lrp to n o ~ , l o n g - t e r m c u l t u r e s w e r e s u c c e s s f u l l y e s t a b l i s h e d f rom t w e l v e t u m o r s by a p p l y i n g e n z y m a t i c d i g e s t i o n or t i s s u e e x p l a n t o f t h e r e s e c t e d t u m o r m a t e r i a l . C y l o g e n e t i c c h a r a c t e r i z a t i o n o f h i t h e r t o t h r e e t u m o r s r e v e a l e d l o s s o f t h e Y c h r o m o s o m e a s s i n g l e c l o n a l a b n o r m a l i t y in two t u m o r s . One t u m o r s h o w e d n o r m a l k a r y o t y p e . C o n c l u s i o n s a b o u t t h e s i g n i f i c a n c e o f l o s s o f t h e Y c h r o m o s o m e in d e v e l o p m e n t a n d / o r p r o g r e s s i o n o f m e t a s t a t i c c a n c e r s e e m p r e m a t u r e . R e m a r k a b l y , t h e two t u m o r s c h a r a c t e r i z e d by l o s s o f t h e Y c h r o m o s o m e w e r e h i s t o p a t h o l o g i c a l l y d i a g n o s e d a s m o d e r a t e l y d i f f e r e n t i a t e d a n d u n d i f f e r e n t i a t e d a d e n o c a r c i n o m a s . T h e o n e w i t h n o r m a l k a r y o t y p e w a s e v a l u a t e d a s m o d e r a t e l y d i f f e r e n t i a t e d . In o r d e r Io a s s e s s t h e e f f e c t s o f c h r o m o s o m a l c h a n g e s on t h e p r o l i f e r a t i o n a c t i v i t y o f p r o s l a t i c t u m o r s , i m m u n o c y t o c h e m i c a l s t u d i e s on t h e t u m o r ce l l c u l t u r e s h a v e b e e n p e r f o r m e d by u s i n g t h e a n t i b o d y K i - 6 7 . Al l t h r e e t u m o r s s h o w e d a p r o l i f e r a t i o n i n d e x in t h e r a n g e o f 1 8 - 2 5 %. Up to now, no c o r r e l a t i o n h a s b e e n f o u n d b e w e e n K i - 6 7 i n d e x a n d t h e e x p r e s s i o n o f E G F - R a n d fos . T h e c o m b i n e d a p p r o a c h o f c y t o g e n e t i c s , m o l e c u l a r g e n e t i c s a n d i m m u n o c y t o c h e m i s t r y m a y h e l p to d e l i n e a t e t h e p a t h o g e n e t i c m e c h a n i s m s in p r o s t a t i c c a n c e r .