Br J Dermatol  2001 Oct;145(4):576-81 

beta-catenin expression in pilomatrixomas. Relationship with beta-catenin gene
mutations and comparison with beta-catenin expression in normal hair follicles.

Moreno-Bueno G, Gamallo C, Perez-Gallego L, Contreras F, Palacios J.

Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas
Carlos III, Instituto de Salud Carlos III, Ctra Majadahonda-Pozuelo Km 2, 280220
Majadahonda Madrid, Spain.

BACKGROUND: beta-catenin functions in signal transduction in the Wnt signalling
pathway, which has recently been implicated in hair follicle (HF) morphogenesis.
beta-catenin gene mutations affecting exon 3 have been reported in a high
percentage of human pilomatrixomas. However, the expression pattern of
beta-catenin in human HFs and pilomatrixomas has not been reported. OBJECTIVES:
To analyse immunohistochemically the expression pattern of beta-catenin in
normal anagen HFs and in 40 human pilomatrixomas. METHODS: In 11 of these
tumours we also studied exon 3 beta-catenin gene mutations by polymerase chain
reaction and direct sequencing. As these mutations have been related to a
replication error (RER) phenotype in other tumour types, we explored whether or
not this association also occurs in pilomatrixomas. RESULTS: beta-catenin was
expressed in the cell membranes of the outer and inner root sheaths and in
matrix cells located at the base and periphery of the HF bulb. However, central
matrix cells that differentiate into cortical cells, cortical and cuticular
cells expressed beta-catenin in the nucleus, suggesting a role in signal
transduction. In addition, some fibroblasts of the dermal papilla also showed
nuclear expression of beta-catenin. All 40 analysed pilomatrixomas showed
intense nuclear and cytoplasmic beta-catenin expression in proliferating matrix
(basaloid) cells. In areas of maturation, transitional cells mainly showed
cytoplasmic and membranous expression of beta-catenin, while only a few cells
retained nuclear expression. Shadow or ghost cells did not show beta-catenin
expression. Three of 11 tumours (26%) had beta-catenin mutations. All three had
the same heterozygote mis-sense mutation: a G to T change affecting the first
nucleotide at codon 32 (D32Y). None of the 11 tumours studied had a positive RER
phenotype. CONCLUSIONS: Present and previous studies suggest that the
Wnt/beta-catenin/Tcf-Lef pathway is activated in normal matrix cells of the HF
to induce differentiation to the hair shaft. Additionally, the beta-catenin
mutation in matrix cells of the HF stabilizes beta-catenin protein, which
translocates into the nucleus, where