162 Infrequent ß-catenin gene mutations in pilomatricomas in Koreans

HJ Lee1, SJ Ha1, JS Kim1, EJ Seo2, HO Kim1, JW Kim1. Dept. of Dermatology1 and Clinical Pathology2, College of Medicine, The Catholic University of Korea, Seoul, Korea.

ß-catenin muations were reported to play a causal role in the deveolpment of pilomatricomas. In a recent study, 75% of pilomatricomas had ß-catenin muations. We investigated the causal role of ß-catenin gene mutations in pilomatricomas of Koreans. This study included 10 formalin-fixed, paraffin-embedded pilomatricomas in Koreans. Basophilic nucleated tumor cells were mirodissected and, as normal controls, infitrating inflammatory lymphocytes were microdissected from the same histologic specimens. Sequencing analysis of exon 3 of the ß-catenin gene was performed. Dinucleotide repeat markers D5S409 and D5S299 were used for PCR-based microsatellite analysis of APC gene. Immunostaining for ß-catenin and Lef-1 was performed by the avidin-biotin-peroxidase method. Sequencing analysis found no mutations in CTNNB1 in 9 samples of pilomatricomas. Only one case had a missense mutation of â-catenin gene at codon 37 from TCT (Ser) to TAT (Tyr). All pilomatricomas revealed intense expression of nuclear Lef-1 and nuclear and cytoplasmic ß-catenin. LOH was observed in 3 out of 5, and in 2 out of 4 informative samples from microsatellite markers D5S299 and D5S409 analysis, respectively. The immunohistochemical results suggest the abnormalities in Wnt-wingless pathway resulting in stabilization or constitutive expression of ß-catenin. The absence of CTNNB1 mutations suggests apc inactivation, or involvements of other components of the wnt-sinaling pathway.