SOX11 Is an Effective Discriminatory Marker, When Used in Conjunction With CK20 and TTF1, for Merkel Cell Carcinoma: Comparative Analysis of SOX11, CK20, PAX5, and TTF1 Expression in Merkel Cell Carcinoma and Pulmonary Small Cell Carcinoma

Abstract

Context.— Distinction between Merkel cell carcinoma (MCC) and pulmonary small cell carcinoma (PSmCC) can be challenging, even with the aid of immunohistochemistry (IHC) analysis of CK20 and TTF1, as these tumors occasionally lack classic immunophenotypes (CK20+/TTF1− in MCC and CK20−/TTF1+ in PSmCC). Objective.— To evaluate the diagnostic utility of SOX11 and PAX5 IHC for distinguishing MCCs from PSmCCs and compare it with that of CK20 and TTF1 IHC. Design.— SOX11, PAX5, CK20, and TTF1 expression (pattern, intensity, and proportion of tumor cells expressing protein) was assessed in 31 primary and 16 metastatic MCCs and 20 primary and 9 metastatic PSmCCs. Results.— SOX11 expression was present in all MCCs and was predominantly strong and diffuse. Only 19% of primary and 38% of metastatic MCCs exhibited diffuse PAX5 expression; none exhibited strong immunoreactivity. Strong and diffuse SOX11 expression was seen in less than 25% of primary and metastatic PSmCCs. PAX5 expression was rare in PSmCCs and was mostly weak and focal/patchy. SOX11 expression in at least 26% of tumor cells, with at least moderate intensity, favored the diagnosis of MCC over PSmCC (P < .001). Furthermore, SOX11 expression was more likely than CK20 expression to be strong or diffuse in sentinel lymph node (SLN) metastases of MCC, indicating that SOX11 is superior to CK20 for detecting tumor deposits in SLNs in MCC. Conclusions.— Our findings indicate that SOX11 not only is a powerful marker for distinguishing MCCs from PSmCCs, especially when used in conjunction with CK20 and TTF1, but also has utility for screening SLNs in MCC.

Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma

“…CC-BY-NC-ND 4.0 International license perpetuity. It is made available under a Upon pyrvinium treatment, the protein activity of several MCC master regulators, including TP53, MYCN, SMADs, and SOX11, exhibited an opposite trend to that previously reported during MCC development (Figure 4B) (19,52,(62)(63)(64)(65). DoRothEA is a generic TF regulon database that is agnostic to cell type.…”