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

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.

Is circulating survivin altered in acromegaly?

“…In contrary to these results, Jankowska et al reported that survivin mRNA expression was 6 fold higher in patients with pituitary adenomas than in controls in one of their study. Moreover, there was not any statistically significance in survivin expression between invasive and non-invasive pituitary adenomas (16). In recent years, various studies have investigated serum survivin levels in many cancer types and revealed conflicting data.…”

“…In addition to studies investiga-ting expression of survivin in various human tumors, there are also some researches investiga-ting survivin expression in somatotroph adenomas to demonstrate its involvement in pituitary tumorigenesis (1,(15)(16)(17)(18). Hovewer, no data are available concerning circulating levels of the survivin in patients with pituitary adenomas.…”

In vivo and in vitro effects of microRNA-27a on proliferation, migration and invasion of breast cancer cells through targeting of SFRP1 gene via Wnt/β-catenin signaling pathway

“…As an antineoplastic factor, miRNA-27a inhibited the Wnt/β-catenin signaling pathway to influence proliferation, migration and invasion ability of glioma cells [21]. The β-catenin signaling pathway was an important part of the Wnt signaling pathway, which influenced the expression of the downstream gene [23]. This proved that Wnt signaling played a fundamental role in the development and maintenance of many organs [24].…”

Limitations of high throughput methods for miRNA expression profiles in non-functioning pituitary adenomas

“…They suggested that WIF1 may be a tumor suppressor, specifically in NFPAs, and the Wnt pathway is important in pituitary tumorigenesis [29]. However, this finding was not validated by other reports showing no activation of canonical and noncanonical Wnt pathway activation in pituitary adenoma [30,31]. Based on these discrepant results further studies are warranted for clarification of the role of miRNAs targeting molecules involved in Wnt signaling in pituitary adenomagenesis.…”