P-GLYCOPROTEIN IS POSITIVELY CORRELATED WITH P53 PROTEIN ACCUMULATIONIN HUMAN COLORECTAL CANCERS

To explore the relationship between mutant p53 and Pgp expression, we have examined the levels of both proteins in human colorectal adenocar cinomas. Serial frozen sections of 40 surgical samples were stained wi th an anti-Pgp (MRK16) and two different anti-p53 protein antibodies ( Abs), PAb421 and PAb1801. Nineteen (47.5%) of 40 samples examined were positive for Pgp, and 18 (45%) of 40 were positive for p53. The sampl es that stained positively with PAb421 also stained positively with PA b1801. Pgp expression was detected in 13 (76.5%) of 17 samples that we re positive for p53 using PAb421 and in 15 (83.3%) of 18 samples that were positive for p53 using PAb1801. Thus, we found that p53 and Pgp w ere co-expressed in a significant number of samples (P<0.002). There w as no relationship between Pgp or p53 protein accumulation and histolo gic grade or stage. The present results demonstrate that Pgp expressio n is closely associated with p53 protein accumulation in human colorec tal cancers. These data provide evidence to support the idea that muta nt p53 activates the MDR1 gene in vivo.