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Expression and Clinical Significance of Wnt Players and Survivin in Pituitary Tumours

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Abstract

Deregulation of the Wnt pathway has been implicated in oncogenesis of numerous tissues including the pituitary gland. Immunohistochemical localization and quantification of β-catenin, Cyclin D1, c-MYC and Survivin expression in 47 pituitary adenomas (35 non-functioning, seven GH-secreting, three prolactinomas, two ACTH-secreting tumour) and six normal controls was undertaken in this study and correlation of protein expression to patient and tumour characteristics analysed. β-catenin was strictly membrane-bound with no difference observed between normal and tumour tissue. In contrast, Cyclin D1 and c-MYC localization was nuclear and significantly higher in tumour versus normal tissue (p < 0.05). c-MYC expression correlated negatively with age at diagnosis (p = 0.006, R = −0.395) while Cyclin D1 expression correlated positively with age (p = 0.036, R = 0.306) and was higher in males than in females (p = 0.036). c-MYC expression was significantly lower in patients with functional tumours requiring octreotide treatment and in patients with non-functioning tumours suffering from hypopituitarism. Survivin expression was extremely low in tumours and absent in normal controls. Involvement of the canonical Wnt pathway appears to be minimal, given the segregation of β-catenin to the membrane. Our data suggest that c-MYC may have an important role in early pituitary tumorigenesis while Cyclin D1 is likely to promote tumour growth at a later stage. We also report a novel gender difference in Cyclin D1 expression, the biological significance of which merits further analysis. The reported reduction of c-MYC in functional tumours subsequently treated with octreotide further supports a role of c-MYC in early tumorigenesis and not in recurrence. The decrease in c-MYC in patients with hypopituitarism provides the first in vivo evidence for hormonal regulation of c-MYC expression.

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Acknowledgements

We would like to thank the Department of Pathology at Mater Dei Hospital for allowing the use of its laboratories and facilities for the purposes of this research.

Declaration of Interest

There are no conflicts of interest between any of the authors or funding bodies.

Funding

This research has been funded by the Malta Government Grant Scheme (vote no. 88-019) and the University of Malta Research Fund Committee Allocation (vote no. PHBRP07-01).

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Authors and Affiliations

  1. Immunohistochemistry Laboratory, Department of Pathology, Mater Dei Hospital, Msida, Malta

    Sharon Falzon, Graziella Santillo & James DeGaetano

  2. Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, Msida, Malta

    Robert Formosa, Mark Gruppetta & Josanne Vassallo

  3. Neuroendocrine Clinic, Mater Dei Hospital, Msida, Malta

    Mark Gruppetta & Josanne Vassallo

  4. Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, Malta

    Angela Xuereb-Anastasi

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  1. Robert Formosa
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  3. Sharon Falzon
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Correspondence to Robert Formosa or Josanne Vassallo.

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Formosa, R., Gruppetta, M., Falzon, S. et al. Expression and Clinical Significance of Wnt Players and Survivin in Pituitary Tumours. Endocr Pathol 23, 123–131 (2012). https://doi.org/10.1007/s12022-012-9197-8

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