Cell-cell adhesion proteins in melanocytic pilomatrix carcinoma

Abstract

Tumors of the matrix of rigid structures include matrical tumors of the hairs, nails, and teeth. These tumors share similar phenotypical and signaling features. Although benign matrical hair tumors are among the most common of these tumors, hair matrix tumors containing pigmented melanocytes are very rare. The malignant variant called melanocytic pilomatrix carcinoma contains benign colonizing dendritic melanocytes admixed with the carcinomatous follicular matrical cells.We studied the expression of cadherins and β-catenin in melanocytic pilomatrix carcinoma because cadherin/catenin-dependent cell-cell adhesion and signals play a critical role in the development of hair and hair tumors. We examined the expression of E- and P-cadherin and the multifunctional protein β-catenin in two cases of melanocytic pilomatrix carcinoma by immunohistochemistry. E- and P-cadherin are expressed at the cell membrane. In contrast, β-catenin is distributed uniformly in the nucleus and cytoplasm of all tumor cells. The diffuse nuclear and cytoplasmic β-catenin expression found in melanocytic pilomatrix carcinomas is indicative of transcriptional activation and β-catenin-induced cell transformation.This is the first report of cadherin/catenin expression in melanocytic pilomatrix carcinoma. Although the study is limited by the number of these rare tumors, the data add information for the understanding of disease mechanisms in hair matrical tumors. Matrical tumors of the hairs share phenotypical features with other matrical tumors and show nuclear translocation of β-catenin, suggesting a transcriptional activating rather than a cellcell adhesion function.

Keywords: cadherins; melanocytic pilomatrix carcinoma; β-catenin.

Figure 1

A, a routine hematoxylin and eosin (H&E) section from the tumor of patient 1, showing a dermal nodule composed of peripheral basaloid cells with central squamous differentiation (bar = 500 µm). B, S-100 staining demonstrating numerous dendritic melanocytes admixed with the epithelial tumor cells (bar = 500 µm). C and D, routine H&E sections showing melanin-pigmented cells (short arrows in C) admixed with the epithelial tumor cells with ghost terminally differentiated squamous cells (long arrow in C). There is marked epithelial cytological atypia and atypical mitoses (short arrows in D) (bar = 125 µm).

Figure 2

A, plasma membrane distribution of E-cadherin (bar = 50 µm) and B, P-cadherin (bar = 500 µm). The overlying epidermis serves as the internal positive control. In contrast, β-catenin is in the nucleus and cytoplasm of all epithelial tumor cells (C and D). Note the plasma membrane distribution of β-catenin in the epidermis in C, which serves as the internal positive control. (Bar = 500 µm in C, and 50 µm in D.)