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Geburtshilfe Frauenheilkd 2001; 61(5): 274-279
DOI: 10.1055/s-2001-14147
Original Article

Georg Thieme Verlag Stuttgart · New York

Expression of Müllerian Inhibiting Substance, CD99 and HEA125 in Ovarian Tumors

Zur Expression von Müller-Gänge inhibierendem Hormon, CD99 und HEA125 in OvarialtumorenF. Kommoss1 , E. Oliva2 , R. H. Young2 , F. Bittinger3 , C. J. Kirkpatrick3 , D. Schmidt1
  • 1 Institut für Pathologie, Referenzzentrum für Gynäkopathologie, Mannheim
  • 2 Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, USA
  • 3 Institut für Pathologie, Universitätskliniken Mainz, Mainz
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Publication History

Publication Date:
31 December 2001 (online)

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Summary

Objective

The expression of Müllerian inhibiting substance (MIS), CD99 (MIC-2 gene product), and HEA125 in ovarian tumors is potentially useful for diagnostic purposes.

Methods

We studied the expression of MIS, CD99, and an epithelial cell-associated antigen recognized by antibody HEA125 in a series of 179 ovarian tumors using monoclonal or polyclonal antibodies and standard immunohistochemical techniques.

Results

MIS was consistently detected in primary and metastatic sex cord tumors with annular tubules (SCTAT) (n = 9). 3 of 9 adult granulosa cell tumors (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 tumors, 1 of 1 gonadoblastoma (sex cord cells positive, germ cells negative), 3 of 8 female adnexal tumors of probable wolffian origin (FATPWO), and 2 of 4 small cell carcinomas of the hypercalcemic type (SCCHCT) were also MIS positive. In contrast, 9 thecomas, 10 fibromas, 10 fibrosarcomas, 8 sclerosing stromal tumors (SST), and 6 Sertoli-Leydig cell tumors (SLCT) were MIS negative. All 11 primary and metastatic JGCT were CD99 positive. In addition, 4 of 13 AGCTs, 3 of 11 thecomas, 3 of 11 SSTs, 3 of 11 SCTs, 2 of 10 SLCTs, 2 of 12 SCTATs, 1 of 1 gynandroblastoma, 1 of 2 unclassified sex cord tumors, and 4 of 12 SCCHCTs were also CD99 positive. However, 11 fibromas, 10 fibrosarcomas, 9 steroid cell tumors, 5 gonadoblastomas, and 10 FATPWOs were 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 borderline or malignant epithelial-stromal tumors were negative. HEA125 immunoreactivity 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 well as in most germ cell tumors and epithelial-stromal tumors. 13 AGCTs, 11 JGCTs, 11 fibromas, 10 fibrosarcomas, 11 SSTs, 12 SCTATs, 1 gynandroblastoma, 9 steroid cell tumors, and 5 gonadoblastomas were HEA125 negative.

Conclusion

Our findings indicate that MIS is a marker of sex-cord differentiation and may be useful as a serum tumor marker for certain sex cord tumors, especially SCTAT. Although the detection of MIS and CD99 in some SCCHCTs and FATPWOs might argue in favor of a sex cord origin, the histogenesis of these tumors remains unclear. Although inhibin-α has previously been shown to be a more sensitive marker of sex-cord differentiation, a panel of immunohistochemical markers including MIS, CD99 and HEA125 may be helpful in the differential diagnosis of certain ovarian neoplasms.

Zusammenfassung

Zielsetzung

Die Expression von Müller-Gänge inhibierendem Hormon (MIS), CD99 und HEA125 ist von potenziellem Nutzen für die Differenzialdiagnostik der Ovarialtumoren.

Methodik

Ein Kollektiv von 179 Ovarialtumoren wurde mit monoklonalen oder polyklonalen Antikörpern und standardgemäßer immunhistochemischer Technik auf die Expression von MIS, CD99 und des epithelialen Markers HEA125 hin untersucht.

Ergebnisse

MIS war durchgehend in 9 primären und metastasierenden Sex cord Tumoren mit Ringtubuli (SCTAT) nachweisbar. 3 von 9 adulten Granulosazelltumoren (AGCT), 4 von 8 juvenilen Granulosazelltumoren (JGCT), 3 von 9 Sertolizelltumoren (SCT), 2 von 2 unklassifizierten Sex cord Tumoren, 2 von 7 Steroidzelltumoren, 1 Gonadoblastom, 3 von 8 Wolff'schen Tumoren (FATPWO) und 2 von 4 kleinzelligen hyperkalzämischen Ovarialkarzinomen (SCCHCT) waren ebenfalls MIS positiv. Demgegenüber waren 9 Thekome, 10 Fibrome, 10 Fibrosarkome, 8 sklerosierende Stromatumoren (SST) und 6 Sertoli-Leydigzelltumoren MIS negativ. Sämtliche 11 primären und metastasierenden JGCT waren CD99 positiv. Zusätzlich waren 4 von 13 AGCT, 3 von 11 Thekomen, 3 von 11 SST, 3 von 11 SCT, 2 von 10 SLCT, 2 von 12 SCTAT, 1 Gynandroblastom, 1 von 2 unklassifizierten Sex cord Tumoren und 4 von 12 SCCHCT CD99 positiv. Andererseits waren 11 Fibrome, 10 Fibrosarkome, 9 Steroidzelltumoren, 5 Gonadoblastome und 10 FATPWO CD99 negativ. Mit Ausnahme fokaler schwacher CD99 Immunreaktivität in 1 von 3 Dottersacktumoren (YST) waren alle 16 sonstigen Keimzelltumoren und sämtliche 18 epithelialen Borderline Tumoren und Karzinome CD99 negativ. HEA125 Expression wurde in 2 von 11 Thekomen, 1 von 11 SCT, 4 von 10 LCT, 1 von 2 unklassifizierten Sex cord Tumoren, 1 von 10 FATPWO, 4 von 12 SCCHCT sowie in den meisten Keimzelltumoren und epithelialen Tumoren nachgewiesen. 13 AGCT, 11 JGCT, 11 Fibrome, 10 Fibrosarkome, 11 SST, 12 SCTAT, 1 Gynandroblastom, 9 Steroidzelltumoren und 5 Gonadoblastome waren HEA125 negativ.

Schlussfolgerung

MIS ist ein Marker der Keimstrangdifferenzierung in Ovarialtumoren und kann potenziell als Tumormarker im Serum für Keimstrangtumoren (insbesondere SCTAT) eingesetzt werden. Wenngleich die Expression von MIS und CD99 in SCCHCT und FATPWO auf eine Herkunft dieser Tumoren von den Keimsträngen hindeuten könnte, bleibt deren Histogenese weiterhin ungeklärt. Obwohl Inhibin-α der im Vergleich zu MIS und CD99 sensiblere Marker für Keimstrangdifferenzierung ist, kann die Kombination der immunhistochemischen Marker MIS, CD99 und HEA125 in der Differenzialdiagnostik bestimmter Ovarialtumoren hilfreich sein.

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Priv.-Doz. Dr. med. F. Kommoss

Institut für Pathologie
Referenzzentrum für Gynäkopathologie
A2,2

68159 Mannheim

Email: gyn-patho@t-online.de