Phosphorylated EGFR (pEGFR T693) as a Novel Predictor of Recurrence in Non-Functioning Pituitary Adenomas

PURPOSE: Non-functioning pituitary adenomas (NFPAs) exhibit high recurrence rates after surgery. However, the determinants of recurrence are inconsistent in the available literature. The present study sought to investigate the association between nuclear phosphorylated EGFR (pEGFR) levels and recurrence of NFPAs. METHODS: Tissue microarrays from patients undergoing adenomectomy for NFPAs at our tertiary care center from 2003 to 2015 and having a minimum of 60 months of follow-up (n=102) were accessed. Immunohistochemical analysis (IHC) was performed to determine the expression of nuclear pEGFR T693. h-score was calculated as the product of staining intensity and the number of positively staining cells. Radiological surveillance (MRI) was performed to categorize NFPAs as recurrent or non-recurrent on follow-up. RESULTS: The mean age of the cohort was 50 ± 11 years with a male preponderance (61.1%). Recurrence was observed in 46.1% of the patients at a median of 123 months (IQR 72-159) of follow-up. pEGFR T693 positivity was higher in a significantly greater number of recurrent NFPAs as compared to non-recurrent NFPAs (95.7% vs 81%, p=0.02). h-scores were also significantly higher in recurrent NFPAs (122.1 ± 6 vs 81.54 ± 3.3, p<0.0001). pEGFR T693 positivity significantly predicted recurrence in NFPAs (HR=4.9, CI 2.8-8.8, p<0.0001). ROC analysis revealed an h-score cutoff of 89.8 as being associated significantly with recurrence (sensitivity 80%, specificity 78%, AUC 0.84, p<0.0001). CONCLUSION: pEGFR T693 was expressed in significantly higher number of recurrent NFPAs. The h-scores were also higher in recurrent NFPAs. Nuclear pEGFR T693 may serve as a predictor of recurrence in NFPAs.