Expression of Cell-Cell Adhesion Molecules in Matrical Tumors of Hairs, Nails, Teeth and Pituitary Gland - Adhesion Molecules - page 305

residues substitution of the GSK-3β-dependent phosphorylation sites causes
inhibition of β-catenin phosphorylation and results in protein stabilization (Sekine
et al. 2003). In contrast to calcifying odontogenic cysts, mutations in β-catenin
were rare in ameloblastomas (Sekine et al. 2003). However, intracytoplasmic and
intranuclear β-catenin was found in ameloblastomas by immunohistochemistry
(Sekine et al. 2003, Kumamoto and Ooya 2005), suggesting epigenetic activation
of β-catenin-dependent signal pathways.
Matrical Pituitary Gland Tumors
During the development of the pituitary gland, remnants of the Rathke's pouch
may give rise to craniopharyngiomas, tumors with a similar phenotype to
calcifying odontogenic cysts and ameloblastomas (Rosai 2004). Moreover, like
most calcifying odontogenic cysts, craniopharyngiomas have been found to
harbor β-catenin mutations, which resulted in stabilization and intranuclear
accumulation of β-catenin (Sekine et al. 2002).
Proposal for a Reclassification of Matrical Tumors of Hard
Adnexal Structures
We propose the grouping of matrical tumors from hair, nails, teeth and pituitary
glands into a single category of neoplasms, regardless of their tissue of origin.
h is is based on phenotypical similarities and the sharing of β-catenin signaling
oncogenic pathways. Most of the matrical tumors from hard tissues and pituitary
gland express nuclear β-catenin at least in the more proliferating, less dif erentiated
basaloid cell compartment (Fig. 3) . h is indicates increased protein stabilization,
upregulation of Wnt signals, disassociation from the cadherin cell-cell adhesion
complex, and activation of its transcriptional factor functions. h ere are, however,
dif erences in the mutation rates of β-catenin between dif erent tumors, indicating
that nuclear β-catenin translocation in some of these tumors may be the result of
upstream signal activation. In the case of onychomatricomas, although the number
of cases is very limited, the i nding of both nuclear and cell membrane β-catenin
and the activation of two dif erent pathways involved in nail development suggest
a spectrum of tumors rel ecting dif erent stages of development mimicry. More
studies are necessary to better dei ne the mechanisms of nail matrix tumor
oncogenesis. Similarly, more detailed dissection of β-catenin signaling in matrical
tumors of the hair, teeth and pituitary gland can provide helpful targets for the
design of better therapeutic strategies.