Abstract
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignancy of the skin. The cell of origin of MCC is thus far unknown and proposed cells of origin include Merkel cells, pro-/pre- or pre-B cells, epithelial stem cells, and dermal stem cells. In this study, we aimed to shed further light on the possibility that a subset of MCC tumors arise from epithelial stem cells of the skin by examining the expression of hair follicle and epidermal stem cell markers in MCC and normal human skin. We also aimed to elucidate any correlation between the expression of these markers and tumor Merkel cell polyomavirus (MCPyV) status or other clinicopathological characteristics or patient survival. Expression of CK19, SOX9, LGR5, and LRIG1 in MCC and normal human skin was studied by immunohistochemistry, and the staining patterns or intensities were statistically correlated with patient, tumor, MCPyV, and survival parameters. In a cohort of 137 cases of MCC, we observed dot-like immunoexpression of CK19 in 30 cases (22.1%) and homogeneous expression in 103 cases (75.7%). We also observed positive immunoexpression of SOX9 in 21 cases (15.3%), LGR5 in 118 cases (86.1%), and LRIG1 in 117 cases (86.0%). Immunoexpression of LRIG1 was found to correlate with better overall and MCC-specific survival. We observed frequent immunoexpression of several hair follicle and epidermal stem cell markers in MCC and found LRIG1 to be a positive prognostic marker in MCC.
Highlights
Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin
We found frequent expression of epithelial stem cell markers in MCC
The expression of epithelial stem cell markers in both MCC and Merkel cells and their progenitors could be explained either by a common ancestor or by MCC developing from Merkel cells
Summary
Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin. We and others have previously shown significant morphologic and Because of their phenotypic similarities, MCC was initially believed to arise from Merkel cells that had undergone malignant transformation. Several arguments against this theory have since been presented, notably that Merkel cells are post-mitotic and that neuroendocrine carcinomas in other organs tend to arise from epithelial progenitors rather than from the neuroendocrine cells themselves [7,8,9]. ATOH1 has been found to be expressed in MCC, and, as such, the acquisition of a Merkel cell-like phenotype in MCC could occur during the oncogenic process [10]. Based on the expression of several B-lymphoid lineage markers in MCC, it has been suggested that the cell of origin for MCC could be a pro-/ pre- or pre-B cell [11]
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