Expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis.

The aim of this study was to identify the pattern and significance of expression of p53 and PCNA in cholangiocarcinoma and primary sclerosing cholangitis. Histological sections from 18 patients with cholangiocarcinoma (3 of the cases were associated with primary sclerosing cholangitis), 10 patients with primary sclerosing cholangitis without cholangiocarcinoma, and 7 patients with cirrhosis without cholangiocarcinoma or primary sclerosing cholangitis were stained immunohistochemically for p53 and PCNA. Samples from 17 patients with cholangiocarcinoma (94%) stained positively for p53. Among these 17 cases, nontumorous bile duct epithelium was positive in 7 (including 3 cases with primary sclerosing cholangitis and 2 with carcinoma in situ), and were positive proliferating bile ductules in 4 cases. The single p53-negative cholangiocarcinoma did not show p53 positivity in either the bile duct epithelium or the proliferating bile ductules. Bile ductal and ductular cells in all 10 patients with primary sclerosing cholangitis without cholangiocarcinoma and in the 7 controls were not reactive for p53. All 18 samples from patients with cholangiocarcinoma (100%) were positive for PCNA protein. Bile duct epithelium was positive for PCNA in nine cases (90%) of primary sclerosing cholangitis without cholangiocarcinoma and in six (85%) controls. Our study showed a high rate of p53 expression (94%) in cholangiocarcinoma. The adjacent uninvolved bile duct epithelium was also immunoreactive for p53 in 7 of 17 patients (41%). These findings suggest an early p53 mutation in bile ductal cells in cholangiocarcinogenesis. Expression of p53 may potentially be used to identify or screen, by bile duct brushings, cases of primary sclerosing cholangitis suspected of harboring cholangiocarcinoma. Expression of PCNA was a universal feature in cholangiocarcinoma.