KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary...

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) require improved diagnostic and therapeutic strategies.
• The epithelial-mesenchymal transition (EMT) is implicated in NF-PitNET pathogenesis.
• E-cadherin (E-Cad) and KLHL14 are key proteins in EMT and were investigated as prognostic markers.

Purpose of the Study:

• To analyze the expression of E-cadherin and KLHL14 as prognostic markers in NF-PitNETs.
• To investigate the subcellular localization of E-Cad and KLHL14 in relation to tumor invasiveness.
• To explore the correlation between protein expression, localization, and clinical outcomes.

Main Methods:

• Immunohistochemistry was used to characterize KLHL14 and E-Cad subcellular expression in 12 NF-PitNET surgical specimens.
• Patients were stratified into low (Ki67 < 3%) and high (Ki67 ≥ 3%) invasiveness groups.
• Protein expression and localization were analyzed in healthy, low-invasive, and high-invasive NF-PitNET tissues.

Main Results:

• KLHL14 expression and nuclear translocation were increased in NF-PitNET tissues compared to healthy tissues.
• Both E-Cad and KLHL14 exhibited a shift from cytoplasmic to nuclear localization with increasing tumor invasiveness.
• Significant correlations were observed between E-Cad/KLHL14 co-localization (cytoplasmic and nuclear) and NF-PitNET invasiveness grade (p=0.01).

Conclusions:

• Nuclear accumulation of E-Cad and KLHL14 in high-grade invasive NF-PitNETs suggests a novel mechanism driving local tumor invasion.
• A trend towards prolonged progression-free survival was noted in patients with lower KLHL14 expression.
• Further studies with larger cohorts are needed to confirm KLHL14's prognostic significance in NF-PitNETs.