Immunohistochemical Diagnosis of Canine Ovarian Epithelial and Granulosa Cell Tumors

Abstract

In humans and canines, the morphology of granulosa cell tumors is extremely variable and causes diagnostic difficulties. In human pathology, immunohistochemistry has been widely used for the diagnosis of granulosa cell tumors, whereas, limited studies are present in canine species. The aim of this study was to investigate the expression of cytokeratins, vimentin, and inhibin-alpha in canine normal ovaries, epithelial ovarian tumors, and granulosa cell tumors to establish an immunohistochemical panel for the differential diagnosis of ovarian tumors. Formalin-fixed, paraffin-embedded tissue sections from 4 normal ovaries, 8 granulosa cell tumors, and 6 epithelial ovarian tumors (2 adenomas and 4 adenocarcinomas) sections were obtained and stained with hematoxylin and eosin and immunohistochemically for cytokeratin AE1/AE3, cytokeratin 7, vimentin, and inhibin-alpha. In normal ovaries, cytokeratin 7, cytokeratin AE1/AE3, and vimentin were expressed in the surface epithelium. Granulosa cells were negative for cytokeratin 7 and displayed variable expression of vimentin, cytokeratin AE1/AE3, and inhibin-alpha toward follicular maturation. Granulosa cell tumors were negative for cytokeratin 7 and positive for inhibin-alpha. Conversely, ovarian epithelial cells tumors were positive for cytokeratin 7 and negative for inhibin-alpha. Both granulosa and epithelial cell tumors displayed variable expression of vimentin. Cytokeratin AE1/AE3 was expressed by all epithelial-derived tumors and 6 of 8 granulosa cell tumors. The results of this study suggest that useful immunohistochemical markers to distinguish epithelial ovarian tumors from granulosa cell tumors are cytokeratin 7 and inhibin-alpha.

Malignant Ovarian Granulosa Cell Tumour in a Ewe

“…Using an antibody that detects a wide spectrum of cytokeratins (CK), positive reaction was found in neoplastic cells in our case; the finding is similar to other authors' observations (Costa et al 1994;Riccardi et al 2007). However, one of the cytokeratins, cytokeratin 7, is selectively expressed in healthy and neoplastic ovarian surface epithelium and is a useful immunohistochemical marker for the differentiation of epithelial ovarian tumours from granulosa cell tumours (Ramaekers et al 1990;Riccardi et al 2007). In our case there was a negative reaction for CK 7.…”

“…However, poorly differentiated granulosa cell tumours may be confused with ovarian epithelial tumours (Pelkey et al 1998;Riccardi et al 2007). Differentiation between these two types of tumours has great prognostic importance, since ovarian epithelial tumours are frequently malignant and metastatic (Riccardi et al 2007). Granulosa cell tumours usually stain positive for α-inhibin, vimentin and calretinin (Ashorn et al 1988;McCluggage and Young 2005;Riccardi et al 2007).…”

“…Vimentin is usually detected in granulosa cell tumours and other ovarian tumours and therefore not a useful marker for differentiation among them (Vang et al 2004;Riccardi et al 2007). Negative immunohistochemical reaction for desmin in this case is in accordance with the results of equal reactions, performed in other cases of granulosa cell tumours (Costa et al 1994).…”

“…Differentiation between these two types of tumours has great prognostic importance, since ovarian epithelial tumours are frequently malignant and metastatic (Riccardi et al 2007). Granulosa cell tumours usually stain positive for α-inhibin, vimentin and calretinin (Ashorn et al 1988;McCluggage and Young 2005;Riccardi et al 2007). Inhibin is a normal glycoprotein secretory product of granulosa cells that decreases pituitary secretion of follicle stimulating hormone (FSH) (Bernard et al 2001) and is known as a sensitive marker for granulosa cell tumours (Pelkey et al 1998).…”

Using of immunocytochemistry in differential diagnosis of neoplasms of serosal cavities in dogs

“…However, simple co-expression of these two intermediate filaments cannot be used as a marker of neoplastic mesothelial cells, since co-expression of cytokeratin and vimentin in the same cells has been detected also in other types of tumors, for example synovial sarcomas, haemangiosarcomas, mammary gland carcinomas (Desnoyers et al 1990, Rabanal andElse 1994). Moreover, co-expression of cytokeratin and vimentin has also been found in tumors which, in cases of dissemination, can be included in differential diagnosis of visceral tumors, among them thyroid carcinomas, prostatic carcinomas, endometrial adenocarcinoma, ovarian epithelial tumors and mammary gland carcinomas (Grieco et al 2003, Riccardi et al 2007, Pires et al 2010. The study performed on the canine lung carcinomas has revealed co-expression of cytokeratin and vimentin in neoplastic cells in 38% of cases (Burgess and Kerr 2009).…”