P53 MUTAGENESIS IN KLATSKIN TUMORS

Mutagenesis of the p53 tumor-suppressor gene represents the most commo n genetic alteration in human malignancies but has not yet been invest igated in Klatskin tumors. Cancerous and normal liver tissues were obt ained from 12 patients after surgical resection of Klatskin tumors. Ge nomic DNA was extracted and served as a template for PCR amplification and sequencing of a 1,574-bp fragment of the p53 gene comprising the exons 5 through 8. Immunohistochemical expression analysis was perform ed using five different antibodies. Missense mutations were detected i n 2 of 12 patients-one transversion on codon 273 (Arg --> Leu) and a t ransition on codon 168 (His --> Arg). In all specimens, immunohistoche mistry was negative regarding a nuclear overexpression. An apparent cl inicopathologic impact of p53 mutations was not observed. This report on mutagenesis of the p53 gene in Klatskin tumors shows that the most commonly mutated tumor suppressor gene in human cancers is also mutate d in a subset of patients with Klatskin tumors. Assessment of a clinic al or pathological impact of p53 mutagenesis on Klatskin tumors requir es evaluation in larger studies. Copyright (C) 1998 by W.B. Saunders C ompany.