Calretinin, a calcium-binding protein, is primarily expressed in certain su
btypes of neurons. It has also been found to be present in mesothelial cell
s and mesotheliomas but not in many types of carcinomas. Using a polyclonal
anti-calretinin antibody, we investigated the expression of calretinin imm
unohistochemically in nonneoplastic human ovaries and testes and ovarian se
x cord-stromal tumors (SCSTs). In ovaries, calretinin was expressed in thec
a interna cells, hilus cells, and scattered individual stromal cells. Oocyt
es, granulosa cells, theca externa cells, rete ovarii, and most stromal cel
ls were negative. Expression of calretinin was also seen in the ovarian sur
face epithelium and in collapsed and flat epithelial inclusion glands (EIGs
), but not in round, columnar, and ciliated EIGs. In some glands, a transit
ion from calretinin-positive to calretinin-negative epithelium was observed
. In postpubertal testes, calretinin was expressed in Leydig cells, but not
in germ cells or most rete testes and Sertoli cells. In ovarian SCSTs, str
ong calretinin staining was seen in all hilus cell tumors (4/4) and the Ley
dig cell component of Sertoli-Leydig cell tumors (10/10). The Sertoli cell
component showed focal weak positivity in 5/10. Fibrothecomas were complete
ly negative (0/8). In granulosa cell tumors, the tumor cells were either co
mpletely negative (8/14) or weakly positive at the periphery of the tumor (
6/14) while scattered stromal cell staining was seen in 9/14 cases. The exp
ression of calretinin in normal Leydig cells, theca interna cells, the Leyd
ig cell component of Sertoli-Leydig cell tumors, and hilus cell tumors sugg
ests its functional relationship with androgen production. Its pattern of e
xpression in ovarian SCSTs is useful in the differential diagnosis of these
tumors. The presence of a transition from calretinin-positive, flat, nonci
liated epithelium to calretinin-negative, columnar, ciliated epithelium in
the same glands provides strong evidence for mullerian metaplasia.