Merkel Cell Carcinomas Possess Telomerase Activity

Summary

Merkel cell carcinomas are believed to be derived from the Merkel cells of the epidermis and hair follicles. The histogenesis of the Merkel cells has not yet been fully elucidated, but several studies suggest that they might originate from an asymmetric cell division of basal keratinocytes or epithelial stem cells of the fetal epidermis, and the resulting differentiated Merkel cells have presumably lost their growth potential.

The capability of indefinite cell division in germ line cells and in the great majority of malignant tumors as well as an increased growth potential in certain somatic cells (such as basal cells of renewable tissues) is correlated with cellular telomerase activity, which is absent in differentiated somatic cells. In this study, the telomerase activity in cryostat sections of frozen Merkel cell tumor biopsies and in in vitro cultivated Merkel cell carcinoma cells was analyzed. The presence of the typical Merkel cell carcinoma phenotype was confirmed in all tumor specimens and cell lines by immunohistochemical staining for the cytokeratin CK 20, which was present in the typical plaque-like distribution. Microdissection was employed on the cryostat sections to concentrate tumor material and to remove potentially telomerase-positive contaminating elements such as epidermis and hair follicles. Telomerase activity was measured by the polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay.

We detected telomerase activity in all four tumors studied and three of four cell lines. Control experiments showed a lack of telomerase activity in normal liver and kidney tissue and telomerase positivity in a breast carcinoma biopsy and activated lymph node, as expected. Immunohistochemistry demonstrated the presence of the catalytic subunit of telomerase in nearly all nuclei of Merkel cell carcinomas.

These results show that despite their pronounced neuroendocrine differentiation and their occurrence in patients of advanced age, Merkel cell carcinomas possess telomerase activity similar to that of common carcinoma types. In future studies, the (difficult) procurement and subsequent analysis of early stages of Merkel cell carcinomas might help to interpret the present findings and to reveal more about the biology of this peculiar type of malignant tumor.