Phospho-fms (p-fms) Expression in Ovarian Sex Cord-stromal Tumors

Summary

Introduction

The macrophage colony stimulating factor receptor (CSF-1 R) is encoded by the c-fms protooncogene. Overexpression of CSF-1 R has been observed to be a poor prognostic factor in epithelial ovarian cancer. Little is known about the significance of CSF-1 R (fms) expression in other ovarian tumors such as sex cord-stromal tumors.

Materials and Methods

Activated CSF-1 R (p-fms) expression was studied immunohistochemically in a series of 59 ovarian sex cord-stromal tumors and miscellaneous tumors using a phosphotyrosine specific antibody and a standard immunoperoxidase technique.

Results

Positive p-fms immunostaining was detected in a majority of sex cord-stromal tumors (6/7 adult granulosa cell tumors, 6/6 juvenile granulosa cell tumors, 2/3 thecomas, 3/3 fibromas, 3/3 sclerosing stromal tumors, 5/5 Sertoli cell tumors, 5/5 Sertoli-Leydig cell tumors, 1/1 gynandroblastoma, 3/5 sex cord tumors with annular tubules, and 5/5 steroid cell tumors). In addition, 3/3 gonadoblastomas, 3/3 endometrioid stromal sarcomas, 4/5 small cell carcinomas of hypercalcemic type, and 4/5 wolffian tumors were also p-fms positive.

Conclusion

Activated CSF-1 R (p-fms) is detectable in most ovarian sex cord-stromal tumors. In contrast to epithelial ovarian cancer, there is no evident correlation between fms overexpression and an aggressive phenotype in sex cord-stromal tumors, since many of the positive tumors are clinically benign.

Zusammenfassung

Einleitung

Makrophagen Kolonie stimulierender Faktor Rezeptor (CSF-1R) wird vom c-fms Protoonkogen kodiert. CSF-1R-Überexpression ist als ungünstiger Prognosefaktor bei epithelialen Ovarialkarzinomen bekannt. Über die Bedeutung der CSF-1R-Expression in anderen Ovarialtumoren, z. B. Keimstrang-Stromatumoren, weiß man bislang wenig.

Material und Methoden

Ein Kollektiv von 59 Keimstrang-Stromatumoren und anderen seltenen Ovarialtumoren wurde immunhistochemisch auf die Expression von aktiviertem CSF-1R (p-fms) hin untersucht. Hierbei kam ein phosphotyrosinspezifischer Antikörper in einem standardgemäßen Immunperoxidase-Protokoll zum Einsatz.

Ergebnis

Positive p-fms-Immunreaktivität wurde in der Mehrzahl aller Keimstrang-Stromatumoren beobachtet (in 6/7 adulten Granulosazelltumoren, 6/6 juvenilen Granulosazelltumoren, 2/3 Thekomen, 3/3 Fibromen, 3/3 sklerosierenden Stromatumoren, 5/5 Sertoli-Zelltumoren, 5/5 Sertoli-Leydig-Zelltumoren, 1/1 Gynandroblastom, 3/5 Keimstrangtumoren mit anulären Tubuli und in 5/5 Steroidzelltumoren). Ebenso waren 3/3 Gonadoblastome, 3/3 endometriale Stromasarkome, 4/5 hyperkalzämische kleinzellige Ovarialkarzinome und 4/5 Wolff'sche Tumoren p-fms positiv.

Schlussfolgerung

Aktivierter CSF-1R (p-fms) ist in fast allen Keimstrang-Stromatumoren des Ovars nachweisbar. Da viele dieser Läsionen klinisch benigne sind, besteht in dieser Tumorgruppe - im Gegensatz zum Ovarialkarzinom - kein offensichtlicher Zusammenhang zwischen fms-Überexpression und aggressivem Phänotyp.

References

• 1 Arceci R J, Shanahan F, Stanley E R, Pollard J W. Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1 regulated placental development.  Proc Natl Acad Sci USA. 1989;  86 8818-8822
• 2 Chambers S K, Kacinski B M, Ivins C M, Carcangiu M L. Overexpression of epithelial macrophage colony-stimulating factor (CSF-1) and CSF-1 receptor: A poor prognostic factor in epithelial ovarian cancer, contrasted with a protective effect of stromal CSF-1.  Clin Cancer Res. 1997;  3 999-1007
• 3 Flick M B, Sapi E, Perrotta P L, Maher M G, Halaban R, Carter D, Kacinski B M. Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody.  Oncogene. 1997;  14 2553-2561
• 4 Kacinski B M, Carter D, Mittal K, Kohorn E I, Bloodgood R S, Donahue J. et al . High level expression of fms proto-oncogene mRNA is observed in clinically aggressive human endometrial adenocarcinomas.  Int J Radiat Oncol Biol Phys. 1988;  15 823-829
• 5 Kacinski B M, Carter D, Mittal K, Yee L D, Scata K A, Donofrio L. et al . Ovarian adenocarcinomas express fms-complementary transcripts and fms antigen, often with coexpression of CSF-1.  Am J Pathol. 1990;  137 135-147
• 6 Kommoss F, Wölfle J, Bauknecht T, Pfisterer J, Kiechle-Schwarz M, Pfleiderer A. et al . Co-expression of M-CSF transcripts and protein, fms (M-CSF receptor) transcripts and protein, and steroid receptor content in adenocarcinomas of the ovary.  J Pathol. 1994;  174 111-119
• 7 Kommoss F, Dittrich M, Hofman-v. Kapp-herr S, Kriegsmann J, Coerdt W, Müntefering H. Ovarian small cell carcinoma, hypercalcemic type. Report of a highly aggressive tumor with uncertain histogenesis.  Elec J Pathol Histol. 1998;  982 11
• 8 Sapi E, Flick M B, Gilmore-Hebert M, Kelly M, Rockwell S, Kacinski B M. Independent regulation of invasion and anchorage-independent growth by different autophosphorylation sites of the macrophage colony-stimulating factor 1 receptor.  Cancer Res. 1996;  56 5704-5712
• 9 Scully R E, Young R H, Clement P B. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament. Atlas of tumor pathology, third series, fascicle 23. Bethesda, Maryland; Armed Forces Institut of Pathology 1998
• 10 Scully R E. Histological typing of ovarian tumors, second edition. World Health Organization International Classification of Tumours. Berlin, Heidelberg, New York; Springer Verlag 1999
• 11 Sherr C J, Rettenmier C W, Sacca R, Roussel M F, Look A T, Stanley E R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1.  Cell. 1985;  41 665-676
• 12 Sherr C J. Conoly-stimulating factor-1 receptor.  Blood. 1990;  75 1-12
• 13 Young R H, Oliva E, Scully R E. Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathologic analysis of 150 cases.  Am J Surg Pathol. 1994;  18 1102-1116