Merkel Cell Carcinoma Display PIEZO2 Immunoreactivity

Abstract

As an essential component of mechano-gated ion channels, critically required for mechanotransduction in mammalian cells, PIEZO2 is known to be characteristically expressed by Merkel cells in human skin. Here, we immunohistochemically investigated the occurrence of Piezo channels in a case series of Merkel cell carcinoma. A panel of antibodies was used to characterize Merkel cells, and to detect PIEZO2 expression. All analyzed tumors displayed PIEZO2 in nearly all cells, showing two patterns of immunostaining: membranous and perinuclear dot-like. PIEZO2 co-localized with cytokeratin 20, chromogranin A, synaptophysin and neurofilament. Moreover, neurofilament immunoreactive structures resembling nerve-Merkel cell contacts were occasionally found. PIEZO2 was also detected in cells of the sweat ducts. The role of PIEZO2 in Merkel cell carcinoma is still unknown, but it could be related with the mechanical regulation of the tumor biology or be a mere vestige of the Merkel cell derivation.

Keywords: PIEZO2; cancer mechanobiology; ion channels; mechanobiology; merkel cell carcinoma; merkel cells.

Figure 1

Single immunohistochemistry for CK20 (a,b), ChrA (c,d), Syn (e,f) and NFP (g,h) was used to characterize MCC cells. They showed two patterns of immunostaining: membranous perinuclear and dot-like. Scale bar 20 µm.

Figure 2

Single immunohistochemistry for CK20 (a,b) and PIEZO2 (c–h) in approximate serial sections showing a perinuclear pattern of distribution identical for both proteins. A detailed examination reveals two patterns of PIEZO2 immunostaining: cytoplasmic with perinuclear halo (e,f) and dot-like (g,h). Scale bars 100 µm (a,c,e,g), 50 µm (b,d), 20 µm (f,h).

Figure 3

Immunofluorescence for PIEZO2, showing its two morphological patterns: cytoplasmic perinuclear (a,b) and dot-like pattern (c,d). Co-localization of PIEZO2 with CK20 (e) or ChrA (f) was regularly observed (merge in yellow). Arrow in ‘f’ indicates a ChrA+/PIEZO2− cell. The MCC cells were processed for simultaneous detection of PIEZO2 and NFP (g–j) only revealed a scarce number of cells showing co-localization of both (i), sometimes resembling MC-nerve contact (arrow in j). Scale bars 50 µm (a,c), 20 µm (b,d–j).

Figure 4

The ductal cells of sweat glands show PIEZO2 immunostaining (a,d) and were densely innervated (b,c,e,f). Scale bar 100 µm.