Purpose: Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary adenomas (NFPA). Here, the expression of two proteins controlling the epithelial-mesenchymal transition (EMT) – an underlying NFPA pathogenic mechanism – were analyzed as prognostic marker: E-cadherin (E-Cad) and KLHL14.
Methods. Immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NFPA patients, with low and high invasiveness grade (respectively, Ki67+ < and ³ 3%).
Results. The analysis of healthy vs NFPA tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad+ and KLHL14+ shifted from a cytoplasmic (C) form in low invasive NFPA to a nuclear (N) localization in high invasive NFPA. Pearson correlation demonstrated the existence of a significant relation between E-Cad/KLHL14 co-localization in cytoplasm (-0,614: p < 0,05) and nucleus (0,729; p < 0,01) and NFPA invasiveness grade.
Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected on high invasive NFPA patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ >3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NFPA patients have to be analyzed to definitively recognize for KLHL14 a key prognostic role.