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.

A case of complete androgen insensitivity syndrome presenting with incarcerated inguinal hernia: an immunohistochemical study

“…The strong nuclear expression of SOX-9 in the Sertoli cells was consistent with its role as a downstream-to-SRY transcription factor, inducing male sex differentiation, including AMH expression (3,4). The focal, weak cytoplasmic expression of PGDS by the Sertoli cells could be attributed to its potentially minor contribution to SOX-9 induction in the presence of a normal SRY gene.…”

“…The following antibodies were used: AMH (Clone 5/6; Serotec, Kidlington, United Kingdom), SOX-9 (Clone H-90; Santa Cruz Biotechnology, Santa Cruz, CA), PGDS (Clone Lipocalin type, murine; Cayman Chemical, Ann Arbor, MI), and AR (Clone AR441; DAKO, Glostrup, Denmark). Immunohistochemical staining was performed using the ChemMate Dako EnVision Detection System, Peroxidase/DAB, Rabbit/Mouse (DAKO) in a DAKO autostainer, as previously described elsewhere (3). Normal testicular tissue was used as a positive control for AR immunostaining.…”

The Oncogenic Roles of DICER1 RNase IIIb Domain Mutations in Ovarian Sertoli-Leydig Cell Tumors

“…Using a laser capture microdissection method, Emerson et al demonstrated that both Sertoli cells and Leydig cells in ovarian SLCTs shared common molecular features at several genomic loci, indicating that they are possibly derived from the same primitive cells during neoplastic transformation [5] . Significant ultrastructural and histologic similarities have been observed between Sertoli cells of SLCTs and neoplastic granulosa cells using electron microscopy and immunohistochemistry [6] , [7] , suggesting that Sertoli cells in SLCTs may derive from primitive cells that normally differentiate into granulosa cells (pregranulosa cells) in the ovarian gonad [8] , [9] . However, it remains unclear how the differentiation of the primitive cells is rewired to stimulate the production of Sertoli and Leydig cells in the ovary.…”

Immunologic Adverse Reaction Associated with Low-carbide Metal-on-metal Bearings in Total Hip Arthroplasty

“…Immunocytochemical analysis of formalin-fixed paraffin-embedded tissue sections was conducted using the ChemMate TM Dako EnVision TM Detection System, horse radish peroxidase (HRP)/diaminobenzidine (DAB), rabbit/ mouse antibody (DAKO, Glostrup, Denmark) in a DAKO autostainer as described previously [26], and included markers of T and B lymphocytes, T suppressor and T helper cells, plasma cells, natural killer (NK) cells, macrophages, and Langerhans' cells. Appropriate positive and negative controls were used for each antibody (Table 3).…”