p53 mutagenesis in klatskin tumors

Abstract Mutagenesis of the p53 tumor-suppressor gene represents the most common genetic alteration in human malignancies but has not yet been investigated in Klatskin tumors. Cancerous and normal liver tissues were obtained from 12 patients after surgical resection of Klatskin tumors. Genomic 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 performed using five different antibodies. Missense mutations were detected in 2 of 12 patients—one transversion on codon 273 (Arg → Len) and a transition on codon 168 (His → Arg). In all specimens, immunohistochemistry was negative regarding a nuclear overexpression. An apparent clinicopathologic 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 mutated in a subset of patients with Klatskin tumors. Assessment of a clinical or pathological impact of p53 mutagenesis on Klatskin tumors requires evaluation in larger studies.