Expression of Cell-Cell Adhesion Molecules in Matrical Tumors of Hairs, Nails, Teeth and Pituitary Gland - Adhesion Molecules - page 304

Moreover, overexpression of Notch1 in transgenic mice causes an increase of
proliferating cells of the nail matrix (Lin and Kopan 2003), forming structures
similar to those seen in onychomatricomas. However, mutations in a gene called
R-sponding4 (RSPO4), an activator of the Wnt/β-catenin signaling pathway,
results in anonychia (autosomal recessive absence of nails) as a result of disruption
of the mesenchymal-epithelial interactions that are crucial in nail development
(Bergmann et al. 2006). h ese i ndings suggest that the Wnt/β-catenin signaling
pathway may be involved in the primary matrix nail development, whereas Notch1
signals may promote the terminal dif erentiation steps in a tissue with continuous
growth. In a case of onychomatricoma we found a distribution of β-catenin
similar to E-cadherin, along the cell membranes as in a cell-cell adhesion role
(Burchette et al. 2008). However, we studied a recent case of onychomatricoma
and found focal intranuclear β-catenin within the less dif erentiated basal layer of
the tumor (Fig. 2A) , suggesting an activated transcriptional role (Peralta Soler and
Burchette, unpublished data). E-cadherin is expressed at the cell membranes in
most epithelial cells of the tumor (Fig. 2B) , whereas P-cadherin, although similarly
distributed at the cell membranes, is more restricted to the epithelial basal layer
(Fig. 2C) . h e i nding of variable nuclear expression of β-catenin in dif erent
onychomatricomas may support the concept that, although there are very few
cases reported of this rare tumor, there may be dif erent variants, rel ecting various
stages of developmental mimicry.
Fig. 2 Immunohistochemical expression of β-catenin and cadherins in the nail matrical tumor
called onychomatrichoma. Expression of β-catenin (A), E-cadherin (B), P-cadherin (C) in an
onychomatricoma. Nuclear β-catenin (arrow) is seen mostly in the basal cells. E- and P-cadherin
show cell membrane distribution (arrows) typical of their cell-cell adhesion function, although
P-cadherin is more restricted to the basal layers. Scale bar = 800 μm in A and 400 μm in B and C.
Matrical Tooth Tumors
h e β-catenin/Wnt signal transduction pathway is crucial for the development of
teeth (Sarkar and Sharpe 1999). Mice dei cient in the β-catenin-interacting LEF1 or
overexpressing Dickkopf1 (dif usible inhibitor of Wnt action) exhibit early arrest in
tooth development (van Genderen et al. 1994, Andl et al. 2002). Somatic β-catenin
mutations were found in most calcifying odontogenic cysts. Serine/threonine