Expression of canonical Wnt proteins and survivin in pituitary tumours

Abstract

Wnt developmental pathways, have been implicated in a number of cancers. Wnt signaling proteins activate the B-catenin transcription factor which induces transcription of the oncogenes Cyclin D1 and Myc (Luo et al. 2007). Elston et al. (2008) found that Wnt inhibitors were down-regulated in pituitary tumours. Overexpression of Survivin, an inhibitor of apoptosis,correlates with poor prognosis and drug resistance (Altieri 2003, Ghosh et al. 2007). Survivin also interacts directly with the aryl hydrocarbon receptor – interacting protein (AIP) mutations of which have been linked with increased susceptibility to pituitary tumour development (Kang & Altieri 2006). The aim of this study was to analyze the expression of B-catenin, Cyclin D1, Myc and Survivin in 40 pituitary adenomas (30 non-functional, 7 acromegalic, 2 prolactinomas, 1 Cushing’s) collected at transphenoidal surgery and 6 normal controls using immunohistochemistry. The results indicate that B-catenin is membrane bound with no difference between normal and tumour tissue, although smaller tumours had higher expression (P<0.05). Cyclin D1 and Myc expression was nuclear and higher in tumour vs normal tissue (P<0.05). Myc expression also increased with lower age at diagnosis (P<0.001, R=0.361) while Cyclin D1 expression was higher in males than in females (P<0.05). Female patients also had overall younger age at diagnosis (P<0.05) and smaller tumours. Expression of survivin was very low in tumours and absent in normal controls. Therefore, involvement of the canonical Wnt pathway appears to be low, since B-catenin was not found located in the nucleus but Myc and Cyclin D1 proteins may play an important role in early pituitary tumorigenesis. Survivin appears to play a minor role owing to its almost complete absence in tumours with <1% of cells showing nuclear staining. Further analysis of the roles of Myc and Cyclin D1 in pituitary tumorigenesis is required.