Expression of Ki-67, p53 and vascular endothelial growth factor (VEGF) concomitantly in growth hormone-secreting pituitary adenomas; which one has a role in tumor behavior ?

OBJECTIVE: In many pituitary tumor, immunohistochemical studies have been shown to be correlated with different aspects of tumor behavior.There is no study up to date in which markers of Ki-67, p53, VEGF were evaluated concomitantly in GH-secreting adenomas.This study aims to determine which marker has a major role in tumor behavior and whether these markers have a cut-off value to distinguish invasive adenoma from non-invasive pituitary adenoma.

METHODS: Fourty-seven acromegalic patients operated by the same neurosurgeon were included in this study.Twenty-one patients(5micro/16 macro) had non-invasive adenomas and 26 had invasive macroadenomas.Eight patients(6 invasive macroadenomas, 2 microadenomas) were treated with OCT-LAR until one month prior to surgery with treatment duration range of 3-11 months.These patients were excluded from the study group as the noninvasive and invasive adenomas were compared.A separate analysis was performed in invasive adenomas to compare OCT(+) and OCT(-)patients.

RESULTS: Both Ki-67 and p53 expressions showed no correlation with the invasive character of adenomas, but VEGF expression in invasive adenomas was significantly higher with respect to noninvasive group.Our study has taken intermediate staining (>25 %)for VEGF as a cut off value for invasive adenomas.It was also observed that the decrease in VEGF staining in OCT pretreated invasive adenomas was significantly more than those not treated with OCT.

CONCLUSION: VEGF becomes an independent stimulator of angiogenic growth and progression for GH-secreting adenomas with >25% cytoplasmic immunoreactivity.This cut-off value may be useful in determination of prognosis and appropriate treatment strategy.A short term preoperative OCT treatment may be useful as adjunctive therapy especially for locally invasive GH- secreting adenomas.