Endocrine Abstracts

Introduction: While there is a significant risk of recurrence in nonfunctioning pituitary adenoma (NFPA) after surgery, it is challenging to predict which NFPAs will recur based solely on routine histopathology. To better understand markers of recurrence, we assessed the established tumor markers linked to aggressive tumor behavior including X-linked IAP (XIAP), the most potent inhibitor of the apoptosis protein family, vascular epithelial growth factor (VEGF) which facilitates angiogenesis and tumour cell proliferation as well as leptin.

Purpose: The purpose of this pilot study was to determine if the expression pattern of select cell proliferation and apoptotic markers in NFA is predictive of tumour quiescence and growth/recurrence compared to normal pituitary tissue in a clinical population.

Methods: Informed consent was obtained from patients during a clinic visit. Tissue microarrays were constructed from paraffin-embedded tissue microarrays (representing pituitary tissues from growing or stable tumours, or normal controls). Immunohistochemical staining using mouse anti-human XIAP monoclonal antibody (BD Biosciences); VEGF monoclonal antibody (Dako); leptin polyclonal antibody (R & D systems) and leptin receptor (Abcam) was completed. Slides were analyzed using Aperio Image Scope-pathology slide viewing software. Chi square and Fishers exact test (P<0.05) were employed.

Results: Tissue samples from 98 patients with NFA (52 males) were analyzed. TMA analysis of normal pituitary tissue (n=24) revealed low levels (weakly positive) of XIAP relative to VEG-F, leptin, and leptin-receptor. VEG-F levels and leptin were moderately positive, while staining for leptin receptor strongly positive in normal pituitary tissue (P<0.0001). XIAP levels in overall tumor tissue revealed moderate and strongly positive staining of XIAP relative to the low staining present in normal pituitary tissue (P<0.00001). VEGF levels in overall tumor tissue were moderately positive in normal pituitary tissue and weakly positive in tumor tissue (P<0.00001). The pattern of leptin and receptor staining in normal tissue was moderately to strongly positive while there was more variability amongst tumor samples (P<0.05). Analyses are ongoing to correlate the pattern of staining with clinical and tumor variables.

Conclusion: Preliminary data show altered expression of markers in tumors compared with normal pituitary tissue. Further clinical data are being analyzed to assess the impact of these changes on recurrence.