Abnormalities of beta-Catenin Gene in Pilomatricomas

Lee, Hyun Jeong; Ha, Seog Jun; Kim, Jung Soo; Lee, Seung Dong; Kim, Jin Wou

Abstract

BACKGROUND: beta-Catenin muations were reported to play a causal role in the development of pilomatricomas. In a recent study in Caucasians, 75% of pilomatricomas had beta-Catenin mutations.
OBJECTIVE
We investigated the causal role of beta-Catenin gene mutations in pilomatricomas of Koreans.
METHODS
This study included 20 formalin-fixed, paraffin-embedded pilomatricomas in Koreans. Basophilic nucleated tumor cells were microdissected and, as normal controls, infiltrating inflammatory lymphocytes were microdissected from the same histologic specimens. Sequencing analysis of exon 3 of the beta-Catenin gene (CTNNB1) was performed. Immunostaining for beta-Catenin and Lef-1 was performed by the avidin-biotin-peroxidase method.
RESULTS
Sequencing analysis found missense mutations (S37Y, S37C, S33C, S33F, and S37F) in CTNNB1 in 6 samples (30%) of 20 pilomatricomas. All pilomatricomas revealed intense expression of nuclear Lef-1 and nuclear and cytoplasmic beta-Catenin.
CONCLUSION
Frequencies of beta-Catenin mutations were lower in our study compared with the results in Caucasians. The immunohistochemical results suggest the abnormalities in Wnt-wingless pathway resulting in stabilization or constitutive expression of beta-Catenin, but the absence of CTNNB1 mutations in 70% of our cases suggests adenomatous polyposis coli gene inactivation, or the involvement of other components of the Wnt-wingless pathway.