Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas.

PURPOSE: The pathogenesis of pituitary adenomas (PA) is complex. Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analysed and correlated with tumour and patient characteristics. METHODS: 74 pituitary tumour samples (48 non-functional PA, 26 functional PAs); Immunohistochemical analysis of protein expression, retrospective analysis of MR images and in vitro analysis of octreotide treatment was carried out on GH3 cells. RESULTS: PTTG expression was negatively associated with age and positively with PA size, regrowth and Ki-67 index. Cyclin D1 correlated with Ki-67 and tumour size. c-MYC negatively correlated with size of tumour and age; and correlated with PTTG expression. Somatostatin analogue treatment was associated with lower Ki-67, PTTG and Cyclin D1 expression while T2 hypointense PAs were associated with lower PTTG, cyclin D1, c-MYC and Ki-67. In vitro analyses confirmed the effect of somatostatin analogue treatment on Pttg and Cyclin D1 expression. CONCLUSIONS: Interesting and novel observations on the differences in expression of tumour markers studied are reported. Correlation between Ki-67 expression, PTTG nuclear expression and recurrence/regrowth of PAs, emphasizes the role that Ki-67 and PTTG expression have as markers of increased proliferation. c-MYC and PTTG nuclear expression levels were correlated providing evidence that PTTG induces c-MYC expression in PAs and we propose that c-MYC might principally have a role in early pituitary tumorigenesis. Evidence is shown that the anti-proliferative effect of somatostatin analogue treatment in vivo occurs through regulation of the cell cycle.

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 ß-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. ß-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 ß-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.

Multifocal peritoneal calcifying fibrous tumour: incidental finding at cholecystectomy.

Calcifying fibrous tumour (CFT) is a benign tumour of elusive aetiology and a potential for local recurrence. Despite its peculiar histological characteristics it can still be confused with interrelated differential diagnosis like inflammatory myofibroblastic tumour (IMT) or solitary fibrous tumours. The clinical differential diagnosis is however much wider. To date seven cases of multiple peritoneal CFTs are on record. The authors present a case discovered incidentally during laparoscopic cholecystectomy, with no previous history and no radiological diagnosis achieved despite having undergone magnetic resonance cholangiopancreatography (MRCP) and normal routine perioperative investigation. The patient is disease-free 12 months after diagnosis. The case report is followed by a detailed literature review.

Testicular mass in an elderly patient: a rare presentation of Hodgkin's lymphoma.

A testicular mass in an elderly man has a high probability of being a lymphoma. However, when the pathologist is faced with a neoplastic lymphoid infiltrate in the testes, one rarely considers Hodgkin's lymphoma as a possibility, as a vast majority turn out to be diffuse large B cell lymphomas. The authors discuss the second case of Hodgkin's lymphoma, nodular sclerosis subtype, presenting as a painless enlarged testicle and associated symptoms similar to irreducible hernia in a 73-year-old gentleman. The patient was later found to have subdiaphragmatic lymph node disease. Hodgkin's lymphoma should therefore be given due consideration in the differential diagnosis of a testicular tumour with a predominantly lymphoid infiltrate.