Expression of Pax7 and Sox2 in pituitary corticotroph adenomas in dogs
Bend, J.E.E. van der
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Cushing’s disease, or pituitary dependent hypercortisolism (PDH), is a common endocrine disease in dogs, caused by a pituitary tumor that produces an excess of the hormone ACTH, which in turn leads to an excess of the hormone cortisol, produced by the adrenal gland. Surgical removal of the pituitary gland by transsphenoidal hypophysectomy has become an important treatment method of Cushing’s disease; recurrence rates turn out to be lower and dogs survive longer than dogs treated with drugs such as Mitotane or Trilostane. The prognosis also depends on the size of the pituitary. Enlarged pituitaries containing a macroadenoma have been shown to have a worse prognosis than non-enlarged pituitaries containing a microadenoma. In search for possible pituitary stem-/progenitor cell populations that may play a role in pituitary tumorigenesis, some progenitor-markers have been identified, among which Pax7 and Sox2. In this study, the expression of transcription factors Pax7 and Sox2 was examined in different canine pituitary (tumor) tissues, by means of immunohistochemistry; microadenomas, macroadenomas, malignant tumors, adenomas in the intermediate lobe of the pituitary and healthy pituitaries were included. Pax7-expression was mainly seen in the IL of the pituitary, but probably also, to a lesser extent, in the anterior lobe (AL). Pax7-expression appeared in clusters of positive cells, but also scattered through the tissue. Sox-expression was mainly seen scattered through the adenohypophysis. In only a minimal number of pituitary samples, Sox2-positivity in the marginal zone could be observed. The overall hypothesis was that Pax7- and Sox2-expression is higher in adenomas and/or malignant tumors than in healthy tissue. Also, it is hypothesized that enlarged adenomas express more of these markers than non-enlarged adenomas. For quantification of Pax7- and Sox2-expression, the percentage of positive cells was scored in each slide, to make comparison between samples possible. Somehow surprisingly, we found a higher expression of Pax7 in healthy pituitary tissue compared to microadenomas (p=0.003) and a higher expression of Pax7 in healthy pituitary tissue compared to malignant pituitary tumors (p=0.036). However, we also found that the expression of Pax7 was significantly higher in macroadenomas than in microadenomas (p=0.007), which is consistent with our hypothesis. No significant differences were found for Sox2 expression when comparing the different groups. More research will be needed to evaluate the correlation of Pax7- and Sox2-expression to clinical parameters such as survival and disease free interval.