Expression of somatostatin receptors, angiogenesis and proliferation markers in pituitary adenomas: an immunohistochemical study with diagnostic and therapeutic implications.
BACKGROUND
Pituitary adenomas are common intracranial neoplasms that generate symptoms as a result of either mass effect or the increased production of pituitary hormones. Although mostly benign, these tumours can be associated with considerable morbidity. We investigated a panel of immunohistochemical preparations to identify potential therapeutic targets and surrogate markers of clinical outcome.


METHODS
Tumour tissue from 25 patients was evaluated for immunohistochemical expression of somatostatin receptors 1‒5, von Willebrand-factor (vWF), interleukin-8 (IL-8), vascular endothelial growth factor receptor 2 (VEGFR-2), kinesin spindle protein (Eg5) and MIB-1 (Ki-67), and its relationship with clinical features was analysed.


RESULTS
The proliferation marker MIB-1 (Ki-67) was the only marker predictive of adenoma recurrence. Of note, 67% of all relapses were associated with tumours showing luteinising hormone expression. All pituitary adenomas showed variable somatostatin receptor, IL-8, Eg5, vWF and VEGFR-2 expression; a relationship between these parameters and clinical outcome could not be demonstrated in this cohort.


CONCLUSIONS
This study validates MIB-1 (Ki-67) as a reliable marker of tumour recurrence in pituitary adenomas. Considering the consistently increased expression of Eg5, IL-8, VEGFR-2, somatostatin receptors and vWF in these tumours, further investigation as potential therapeutic targets is warranted.
Institute of Neuropathology, University Hospital of Zurich, Switzerland; alejandra.magagna@gmail.com.
Alejandra
A
Magagna-Poveda
Henning
H
Leske
Christoph
C
Schmid
René
R
Bernays
Elisabeth J
EJ
Rushing
D000236:Adenoma / Q000378:metabolism* / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000628:therapy; D011379:Prognosis; D017481:Receptors, Somatostatin / Q000378:metabolism*; D012189:Retrospective Studies; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
D014408:Biomarkers, Tumor; C508606:CXCL8 protein, human; D016209:Interleukin-8; C470243:KIF11 protein, human; D019394:Ki-67 Antigen; D017481:Receptors, Somatostatin; D014841:von Willebrand Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D016547:Kinesins