Erythropoietin (EPO) is a well-recognized hormone that induces erythro
cytosis in a wide range of physio-logic and pathologic situations in m
ammals. One of these situations is a paraneoplastic erythrocytosis, wh
ich might be seen in association with various neoplasms, including ren
al cell carcinoma (RCC), hepatoma, and cerebellar hemangioblastoma Alt
hough there have been multiple studies confirming the association betw
een this erythrocytosis and the production of EPO by tumor cells, immu
nohistochemical detection of EPO in formalin-fixed, paraffin-embedded
tissue was not described, We report on the use of microwave antigen re
trieval to detect EPO in RCCs in such routinely processed tissues, We
selected 19 RCCs received as nephrectomy specimens, fixed in formalin,
and routinely processed, These cases were previously diagnosed on the
basis of morphologic, immunohistochemical, and clinical features. We
examined the immunoreactivity of these specimens with a monoclonal ant
i-EPO antibody, Fetal (20 wk gestational age) liver served as a positi
ve control, Intense positive immunoreactivity was observed as cytoplas
mic, granular staining in fetal hepatocytes, Fourteen RCCs (10 clear c
ell and 4 tubulopapillary types) demonstrated unequivocal cytoplasmic
immunoreactivity,Additionally, two clear cell tumors were only focally
positive, whereas three (16%) were negative, EPO immunoreactivity mig
ht thus prove to be of value in the diagnosis or confirmation of RCC,
particularly in the context of routinely processed material.