Expression and clinical significance of Wnt players and survivin in pituitary tumours.
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.
Department of Medicine, Faculty of Medicine and Surgery, Mater Dei Hospital, University of Malta, Msida, Malta. robert.formosa@gmail.com
Robert
R
Formosa
Mark
M
Gruppetta
Sharon
S
Falzon
Graziella
G
Santillo
James
J
DeGaetano
Angela
A
Xuereb-Anastasi
Josanne
J
Vassallo
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015175:Prolactinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012737:Sex Factors; D000077022:Survivin; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016271:Proto-Oncogene Proteins c-myc; D000077022:Survivin; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D015282:Octreotide