title: Investigating differentiation mechanisms of the constituent cells of sex cord-stromal tumours of the ovary.
abstract: SOX-9, an essential factor for male sexual development, can be induced by prostaglandin D2 in a Sry-independent mechanism. Recent data suggest that the hedgehog pathway is involved in the differentiation of normal Sertoli and Leydig cells. The purpose of our study was to investigate the mechanisms involved in the differentiation of ovarian sex cord-stromal tumour (SCST) cells. Two Sertoli-Leydig cell tumours and two granulosa cell tumours with a minor Sertoli element were studied using immunohistochemistry on paraffin-embedded tissue sections. Sertoli cells expressed anti-Mullerian hormone (AMH), SOX-9, prostaglandin D synthase (Pgds) and bcl-2 (in four of four cases); sonic hedgehog (Shh) and p53 (in three of four cases) and androgen receptors (AR; in one of four cases). Ki-67 index ranged from 10% to 50%. Leydig cells expressed Shh and AR (two of two cases), while they showed no expression of p53, bcl-2 and 0% Ki-67 index. Granulosa cells expressed AMH, Pgds, Shh, estrogen receptors, progesterone receptors, AR and bcl-2 (in two of two cases) and p53 (in one of two cases). Ki-67 index was 10% and 40%, respectively. Further investigation is required to clarify the role of the molecules outlined above in the histogenesis of ovarian SCST, as Pgds-mediated SOX-9 upregulation could provide a reasonable explanation for the presence of testicular differentiation in ovarian SCST.
authors.affiliation: Department of Pathology, General Hospital Agios Andreas, Patras, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Papanastasopoulos
authors.forename: Maria
authors.initials: M
authors.lastname: Repanti
authors.forename: Vasileia
authors.initials: V
authors.lastname: Damaskou
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Bravou
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D005260:Female; D006106:Granulosa Cell Tumor / Q000378:metabolism / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D054834:Lipocalins / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012189:Retrospective Studies; D055758:SOX9 Transcription Factor / Q000378:metabolism; D018310:Sertoli-Leydig Cell Tumor / Q000378:metabolism / Q000473:pathology*; D018312:Sex Cord-Gonadal Stromal Tumors / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D054834:Lipocalins; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; C509239:SHH protein, human; D055758:SOX9 Transcription Factor; D016159:Tumor Suppressor Protein p53; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase