P53 PROTEIN IMMUNOREACTIVITY IN EXTRAHEPATIC BILE-DUCT AND GALLBLADDER CANCER - CORRELATION WITH TUMOR GRADE AND SURVIVAL

Forty-five extrahepatic bile duct carcinomas (i.e., tumors of the regi on proximal to the duct junction, including Klatskin tumors, tumors of the lower mid-region, and tumors of the ampulla of Vater) and 11 gall bladder carcinomas were immunohistochemically examined for p53 protein expression, using the DO-7 monoclonal (mAb) and the CM-1 polyvalent ( pAb) antibodies and an antigen retrieval method. Because the DO-7 mAb was found to be significantly more reliable than the CM-1 pAb in detec ting p53 immunoreactivity, the immunohistochemical results obtained wi th the former antibody were used for comparing p53 protein immunoreact ivity with tumor site, tumor grade, and survival of patients. Approxim ately one third (3 of 10) of the proximal tumors were found to express weak p53 immunopositivity, whereas moderate immunopositivity and high er rate (18 of 29) was observed in tumors of the lower mid-region. Fin ally, moderate and marked p53 immunopositivity was observed in tumors of the ampulla (5 of 6) and gallbladder (8 of 11). In tumors of the lo wer mid-region of the ampulla and the gallbladder, a significantly hig her p53 positivity was noted in high-grade compared with low-grade neo plasms. For the cases in which complete follow-up was available (11 tu mors of the low mid-region), median survival of patients with p53-nega tive tumors was 25.7 months, whereas survival of those with p53-positi ve tumors was 5.2 months. In conclusion, our findings suggest that (1) p53 protein is differentially expressed in extrahepatic bile duct car cinomas, thus stressing the clinical and histological distinction betw een proximal and lower duct tumors, (2) in a subset of the above carci nomas, p53 protein expression appears to be related to higher grades o f malignancy, and (3) the presence of p53 immunopositivity might be as sociated with a shorter survival of the patients.