ALTERATIONS OF THE P53 TUMOR-SUPPRESSOR GENE AND K-RAS ONCOGENE IN PERIHILAR CHOLANGIOCARCINOMAS FROM A HIGH-INCIDENCE AREA

We observed a clustering of cholangiocarcinoma in a part of West Virgi nia. We analyzed the frequency and type of alterations in the p53 tumo r-suppressor gene and the K-ros oncogene to determine whether cholangi ocarcinomas from this high-incidence area differ from other cholangioc arcinomas at the molecular level. We studied IZ carcinomas of patients from the high-incidence area (West Virginia group), and 15 carcinomas of patients from nearby states (non-West Virginia group). Over-expres sion of the p53 gene product, accompanying most mutations in the p53 g ene, was determined by immunohistochemistry. p53 sequence analysis of exons 5, 6, 7, and 8 of the p53-immunohistochemical-positive carcinoma s was also performed. K-ros codon IZ mutations were detected by the po lymerase chain reaction and allele-specific oligonucleotide hybridizat ion. Significantly more cholangiocarcinomas from the West Virginia gro up were p53-immunohistochemical-positive than from the non-West Virgin ia group (67% vs. 20%; p < 0.05), p53 mutations did not differ in the 2 groups in respect to site or specific type. No differences were foun d between the 2 groups regarding K-ros mutations (17% vs. 27%). Althou gh the higher frequency of p53-immunohistochemical positivity in the W est Virginia group may reflect a different etiology of these cholangio carcinomas, explaining the high incidence in this area, results of p53 sequence analysis were not different in the West Virginia group. The high incidence may be explained by difference in carcinogenic dose or a different etiology not reflected in p53 or K-ros alterations. (C) 19 98 Wiley-Liss, Inc.