Inhibition of apoptosis is a critical step in tumorigenesis in many cancers, 
including Merkel cell carcinoma; however, the exact regulatory mechanisms are 
not fully understood. Survivin is an inhibitor of apoptosis that is undetectable 
in most terminally differentiated normal human tissues, strongly expressed in 
embryonic and fetal organs and is strongly expressed in many different human 
cancers. In this study, we investigated the expression of survivin in cutaneous 
Merkel cell carcinoma using immunohistochemistry and correlated the findings 
with long-term clinical follow-up. We collected and immunostained 19 cases of 
Merkel cell carcinoma with antibodies to survivin. The median patient age was 79 
years, with an average follow-up of 17 months, and a male/female ratio of 7:11. 
All but one sample represented primary lesions and two cases were obtained from 
one patient. Clinical follow-up was obtained in 15 cases (79%). All 19 cases of 
Merkel cell carcinoma demonstrated strong immunoreactivity for survivin. 
Survivin protein was localized and classified into predominately nuclear (N=8) 
or cytoplasmic (N=4) compartments. A mixed pattern of survivin expression was 
also seen in three cases. Cases with a nuclear staining pattern were 
distinguished by an aggressive clinical course, with seven of eight patients 
developing metastases or dead of disease on follow-up. Furthermore, all of the 
cases with predominately cytoplasmic survivin localization (N=4) were free of 
disease on follow-up. Merkel cell carcinomas represent aggressive malignancies 
regulated by apoptotic pathways. We demonstrate that survivin, a protein with a 
dual role in inhibition of apoptosis and regulation of cellular proliferation is 
expressed in Merkel cell carcinoma. Moreover, nuclear subcellular localization 
of survivin in Merkel cell carcinomas may portend a poor prognosis and 
identification of these cases may assist clinical management.