Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors

Merkel cell carcinoma

“…The relatively frequent association between MCC and cutaneous squamous cell carcinoma could be explained by both tumours originating from a common multipotent stem cell, divergent differentiation of neoplastic cells or simultaneous growth of two unrelated malignancies. Overexpression of p53 has been observed in combined tumours 92 . MCC has been occasionally found at the same site as other benign or malignant tumours, but these cases probably represent chance associations.…”

Comment on “Diffuse TTF-1 expression in a case of Merkel cell carcinoma”

“…In our report, TTF-1 expression was present to a variable extent in 4/5 (80%) cases, and peculiarly in two cases also in the squamous cell carcinoma component [1]. Combined MCC differs in many aspects from the conventional MCC: being Merkel cell polyomavirus (MCPV) negative, showing high expression of p53 and a low level of Rb1 and a much higher number of mutations [4,5,6]. MCPV-negative MCCs overlap to some extent in biology and genetics with the combined MCC, as they present TP53 mutations and a high mutation phenotype, with the majority of them showing a UV-signature pattern with C > T transitions [5,7,8].…”

“…Combined MCC differs in many aspects from the conventional MCC: being Merkel cell polyomavirus (MCPV) negative, showing high expression of p53 and a low level of Rb1 and a much higher number of mutations [4,5,6]. MCPV-negative MCCs overlap to some extent in biology and genetics with the combined MCC, as they present TP53 mutations and a high mutation phenotype, with the majority of them showing a UV-signature pattern with C > T transitions [5,7,8]. As all TTF-1-positive conventional MCCs developed in very old people in sun-exposed areas (85, M, right frontal scalp [9], 84, lower lip [3], 74, F, right lower leg [10], 88, F, upper lip [11]), we speculate that TTF-1 expression may correlate with chronic UV light exposure but not with MCPV etiology.…”

Merkel Cell Carcinoma

“…16 These cases are more highly represented among the CK20-negative MCC population and have been shown to uniquely express follicular stem cell markers 17 and higher labeling with p53. 16,18 …”

“…Evidence builds, however, that MCC with squamous differentiation is clinically different and harbors histologic and molecular signatures, similar to CK20-negative MCC, 32 of UV-related squamous epithelial tumors. 4,16,17 Such tumors show less CK20 and NF positivity and more p53 and follicular stem cell markers 16–18 and are always negative for MCV. Well-differentiated SCC is easily diagnosed.…”