P53 EXPRESSION IS ASSOCIATED WITH A HIGH-DEGREE OF TUMOR DNA ANEUPLOIDY AND INCIDENCE OF P53 GENE MUTATION, AND IS LOCALIZED TO THE ANEUPLOID COMPONENT IN COLORECTAL CARCINOMAS

p53 protein expression was studied by immunoblotting in 34 colorectal carcinomas and 28 of the corresponding normal mucosas, and correlated with tumor DNA ploidy as measured by flow cytometry. p53 protein was d etected in 35% (12/34) of the tumors; the normal mucosas were negative . Fifty-five percent (12/22) of the tumors examined for mutations with in the four hotspots (exons 5-8) of the p53 gene had point mutations. p53 expression correlated significantly with the presence of p53 gene mutations; 67% (8/12) of the tumors with mutations expressed p53, wher eas only one of 10 tumors where no mutations were detected expressed t he protein (p=0.01). Four tumors with p53 gene mutations did not expre ss p53. Fifty-nine percent (20/34) of the tumors were aneuploid. p53 e xpression correlated significantly with aneuploidy; a total of 55% (11 /20) of the aneuploid tumors were positive for p53 compared to 7% (1/1 4) of the diploid tumors (p=0.009). All of the 11 highly aneuploid tum ors (1.31 less-than-or-equal-to DNA index (DI); less-than-or-equal-to 1.86) expressed p53, whereas all of the 9 moderately aneuploid tumors (1.11 less-than-or-equal-to DI less-than-or-equal-to 1.29) were p53-ne gative. Flow cytometry was also used to resolve cell cycle- and ploidy specific p53 expression in nuclei in 4 aneuploid tumors. p53 expressi on in these tumors was confined to the aneuploid component, whereas th e diploid component was negative. p53 was seen in nuclei in all phases of the cell cycle of proliferating aneuploid cells. Neither p53 expre ssion nor tumor DNA ploidy were correlated with Dukes' stage (p=1.00 a nd 0.72, respectively). The data suggest that high levels of mutant p5 3 may play a causative role in the generation of highly aneuploid tumo rs.