6th ESACP Congress, Heidelberg, April 7-11, 1999

A066
NUMERICAL ABERRATIONS OF THE P53-GENE IN BREAST TUMOR CELLS WITH DIFFERENT DNA CONTENT
Haroske G, Friedrich K, Dimmer V, Illmer T*, Kunze KD

Institute of Pathology, * Department of Internal Medicine, Dresden University of Technology, Germany

Aim: Quantitative and qualitative changes in p53 may lead to an accumulation of genetic aberrations in the cells affected. At a certain degree those aberrations are detectable cytometrically as DNA aneuploidy. The study was aimed at the analysis of numerical aberrations of the p53 gene locus in relation to the centromere of chromosome 17 and the DNA ploidy of the tumor as to study the heterogeneity of p53 changes in that cancer type. Methods: Tumor imprints of 35 breast cancers (8 peridiploid, 8 peritetraploid, 18 aneuploid) were subjected to a two-color FISH technique with DNA probes for the centromere 17 and the p53 gene locus. FISH spots were counted in at least 120 tumor cells and up to 10 lymphocytes in each imprint. The DNA ploidy of the tumors was detected by Feulgen DNA image cytometry, the expression of p53, Ki-67, and WAF-1 was studied by immunohistochemistry. By means of SSCP mutations were searched in the exons 5 to 8 of the p53 gene. Results & Conclusions: In peritetraploid and aneuploid tumors numerous p53 aberrations were found, accompanied by a strong intratumoral heterogeneity of the aberration pattern in the single cells. Besides deletions gains of gene loci were found in those tumors, too. However, in p53 expression and in the proliferation rate the peritetraploid tumors were not different from the peridiploid ones. An evolution from the peridiploid to the peritetraploid and aneuploid tumors seems to be obvious, in which the p53 plays an important but not the decisive role.