ABSTRACT
E-and P-cadherin are crucial in determining the formation and maintenance of the epidermis and the skin adnexae, including the hair follicles (Hirai et al. 1989). Th e hair cycles during the lifespan of mammals, although there are specifi c time and regulatory diff erences in diff erent parts of the body and between species (Camacho et al. 2000). Th e maximal growth phase of the hair is called the anagen stage. During this period, E-cadherin is expressed in the outer and inner root sheaths and in the outer portion of the hair matrix, and P-cadherin is expressed in the innermost portion of the hair matrix near the dermal papilla (Hardy and Vielkind 1996, Muller-Rover et al. 1999). Functional P-cadherin induces the segregation of proliferating hair matrix cells to form a follicular epithelial unit (Muller-Rover et al. 1999), and its absence interferes with the normal hair cycle. Mutations in the CDH3 gene encoding P-cadherin cause the autosomal recessive disorder called ectodermal dysplasia-ecterodactyly-macular dystrophy, manifested by sparse scalp hair and blindness (Sprecher et al. 2001). During the formation of the hair follicle, primitive mesenchymal cells aggregate to form the dermal papilla and release Wnt signals, which in turn prevent the degradation of β-catenin. Stable β-catenin acts as a transcription factor and activates LEF1 (lymphocyte enhancing factor 1) and downregulates E-cadherin. Th e process can be reversed by forced elevation of E-cadherin, which results in interruption of the development of normal hair follicles (Jamora et al. 2003). In the adult hair follicle, β-catenin is expressed inside the nucleus of inner hair matrix cells and in the cell membranes of the outer and inner root sheaths (Jamora et al. 2003). Th is diff erential pattern of expression of β-catenin suggests a switch from a transcriptional factor role (Behrens et al. 1996) in hair matrix cells during development to a structural role as part of the cadherin-catenin cellcell adhesion complex in the diff erentiated cells of the adult hair follicle. Th is diff erential distribution of cadherins and β-catenin is also seen in the diff erent portions of hair matrical tumors such as pilomatricoma, melanocytic matricoma (Peralta Soler et al. 2006) and pilomatrix carcinoma (Hassanein and Glanz 2004). In melanocytic matricoma, the less diff erentiated basaloid cells express nuclear and cytoplasmic β-catenin (Fig. 1A). Th is is consistent with the transcriptional role of β-catenin in these cells and refl ects the frequent activating mutations in exon 3 of CTNNB1, the gene encoding for β-catenin, found in both benign (Chan et al. 1999) and malignant (Lazar et al. 2005) pilomatricomas. In contrast, the more diff erentiated squamoid cells express cell membrane β-catenin together with E-cadherin (Fig. 1B). P-cadherin is expressed at the cell membrane but restricted to the basaloid cells and is absent from the anucleated fully diff erentiated keratinized shadow cells (Fig. 1C). Th e tumor is colonized by numerous HMB-45 (a marker of melanosomes) positive dendritic cells (Fig. 1D), which gives it its name.
