ErbB2 and EphA3 as a novel prognostic and therapeutic target of Recurrent Non-functioning Pituitary Adenomas: A pilot study

Abstract

Non-functioning pituitary adenomas (NFPA) are 30% of all pituitary adenomas. Although benign in nature but they may be invasive and recurrent. Markers of recurrence are needed to guide patient management. Recteptor Tyrosine Kinases (RTK) may sereve as therapeutic marker for recurrence as they can targeted by already available tyrosine kinase inhibitors. To examine differential RTK phosphorylation pattern of recurrent NFPAs, we recruited 20 patients and grouped them as non-recurrent (n=10), and recurrent (n=10). Recurrence was determined by follow-up of 15 years. We then performed a membrane-based antibody array (ARY001B) for the determination of the relative phosphorylation of 49 tyrosine kinases in recurrent NFPAs. As the experiment was replicated on two set of membranes, each tyrosine kinase was represented in quadruples. Student’s t-test was performed to compare the means between two groups. We found ErbB2, PDGFR beta, SCFR, Trk, VEGFR1, VEGFR2, EphA3, and Alk significantly hyperphosphorylated in recurrent NFPAs. Out of these eight hyperphosphorylated tyrosine kinases ErbB2 and EphA3 were 1.6 (p=0.01) and 1.9 (p=0.002) times hyperphosphorylated in recurrent NFPAs. This result indicates that EphA3 may be an effective therapeutic target in recurrent NFPAs.