Objective: The expression of Mullerian inhibiting substance (MIS), CD99 (MI
C-2 gene product), and HEA125 in ovarian tumors is potentially useful for d
iagnostic purposes.
Methods: We studied the expression of MIS, CD99, and an epithelial cell-ass
ociated antigen recognized by antibody HEA125 in a series of 179 ovarian tu
mors using monoclonal or polyclonal antibodies and standard immunohistochem
ical techniques.
Results: MIS was consistently detected in primary and metastatic sex cord t
umors with annular tubules (SCTAT) (n=9). 3 of 9 adult granulosa cell tumor
s (AGCT) 4 of 8 juvenile granulosa cell tumors (JGCT), 3 of 9 Sertoli cell
tumors (SCT), 2 of 2 unclassified sex cord tumors, 2 of 7 steroid cell tumo
rs, 1 of 1 gonadoblastoma (sex cord cells positive, germ cells negative), 3
of S female adnexal tumors of probable wolffian origin (FATPWO), and 2 of
4 small cell carcinomas of the hypercalcemic type (SCCHCT) were also MIS po
sitive. In contrast, 9 thecomas, 10 fibromas, 10 fibrosarcomas, S sclerosin
g stromal tumors (SST), and 6 Sertoli-Leydig cell tumors (SLCT) were MIS ne
gative. All 11 primary and metastatic JGCT were CD19 positive. In addition,
1 of 13 AGCTs, 3 of II thecomas, 3 of II SSTs, 3 of 11 SCTs, 2 of 10 SLCTs
, 2 of 12 SCTATs, 1 of 1 gynandroblastoma, 1, of 2 unclassified sex cord tu
mors, and 4 of 12 SCCHCTs were also CD99 positive. However, 11 fibromas, 10
fibrosarcomas, 9 steroid cell tumors, 5 gonadoblastomas, and 10 FATPWOs we
re CD99 negative. Likewise, except for weak focal CD99 immunostaining in 1
of 3 yolk sac tumors (YST), all 16 remaining germ cell tumors and all 18 bo
rderline or malignant epithelial-stromal tumors were negative. HEA125 immun
oreactivity was detected in 2 of 11 thecomas, 1 of 11 SCTs, 4 of 10 SLCTs,
1 of 2 unclassified sex cord tumors, 1 of 10 FATPWOs, 4 of 12 SCCHCTs as we
ll as in most germ cell tumors and epithelial-stromal tumors. 13 AGCTs, 11
JGCTs, 11 fibromas, 10 fibrosarcomas, 11 SSTs, 12 SCTATs, 1 gynandroblastom
a, 9 steroid cell tumors, and 5 gonadoblastomas were HEA125 negative.
Conclusion: Our findings indicate that MIS is a marker of sex-cord differen
tiation and may be useful as a serum tumor marker for certain sex cord tumo
rs, especially SCTAT. Although the detection of MIS and CD99 in some SCCHCT
s and FATPWOs might argue in favor of a sex cord origin, the histogenesis o
f these tumors remains unclear. Although inhibin-cr has previously been sho
wn to be a more sensitive marker of sex-cord differentiation, a panel of im
munohistochemical markers including MIS, CD99 and HEA125 may be helpful in
the differential diagnosis of certain ovarian neoplasms.