Expression analysis of Pax7 and Sox2 in canine pituitary gland adenomas and correlation with clinical parameters
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Cushing’s disease or pituitary-dependent hypercortisolism(PDH) is a common endocrinologic disorder in dogs. In 80% to 85% of cases of hypercortisolism, the cause is a pituitary gland adenoma. The pituitary adenoma mostly arises from the adenohypophysis (75% to 80%)and in the other cases from the pars intermedia. The diagnosis of Cushing’s disease is based on urinary cortisol/creatinine ratios (UCCRs) combined with a high dose dexamethasone suppression test (HDDST). Without treatment the life expectancy of dogs with Cushing’s disease is less than one year.1 There are different therapeutic options for dogs with Cushing’s disease. Medical treatment is possible with Mitotane or Trilostane. Also surgery is a treatment option, than the complete pituitary gland is removed by transsphenoidal hypophysectomy. However, even after initial remission of the disease, long- term recurrence does occur. The pathogenesis of pituitary gland adenomas is largely unknown. It is thought that so called cancer stem cells play a role in tumorigenesis. When such cells can be identified, new therapeutic strategies, directed at these stem cells, could be developed. To identify potential cancer stem cells in the pituitary gland, certain markers can be used. Transcription factors Sox2 and Pax7 are possible stem cell marker. They are both transcription factors that are thought to play a role in pituitary development and tumorigenesis. In this research project the expression of the markers Pax7 and Sox2 in pituitary gland adenomas was investigated. Positive Pax7 and Sox2 cells are counted with ImageJ and the labeling indices were calculated. The expression was correlated with clinical parameters such as, tumor type, the size of the pituitary gland, disease free interval of the dog, survival time of the dog and recurrence of Cushing’s disease after surgery. No significant difference was found when the expression of Pax7 and Sox2 is compared between different groups of clinical parameters, like non-enlarged and enlarged. However, the survival time of the patients shows that there was a positive correlation between the expression of Sox2 and the survival time. No significant difference was found in the survival analysis when the survival time of Pax7 positive patients and Pax7 negative patients were compared and when patients with low Sox2 expression and patients with high Sox2 expression were compared. In conclusion, more research is necessarily to investigate if there is a relation between the expression of these markers and their role in tumorigenesis and their relation with clinical parameters.