Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours

Abstract

Purpose Clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs) present a varying degree of aggressiveness, and reliable prognostic markers are lacking. We aimed to characterise the distribution of E- and N-cadherin in corticotroph, PIT1 and null-cell NF-PitNETs, and link it to the course of the tumours. Methods The distribution of E- and N-cadherin was investigated by immunohistochemistry in a retrospective cohort of 30 tumours of the less common NF-PitNETs (corticotroph (N = 18), PIT1 (N = 8) and null-cell PitNETs (N = 4)). Immunoreactive scores (IRS) were compared to previously presented cohorts of gonadotroph NF-PitNETs (N = 105) and corticotroph functioning PitNETs (N = 17). Results We found a low IRS for the extra-cellular domain of E-cadherin (median 0 (IQR 0–0, N = 135)), a medium to high IRS for the intra-cellular domain of E-cadherin (median 6 (IQR 4–9)) and a high IRS for N-cadherin (median 12 (IQR 10.5–12)) throughout the cohort of NF-PitNETs. The corticotroph NF-PitNETs presented a higher IRS for both the extra- and intra-cellular domain of E-cadherin (median 0 (IQR 0–1) and median 9 (IQR 6–12), respectively) than the gonadotroph NF-PitNETs (p < 0.001 for both comparisons). Presence of nuclear E-cadherin was associated with a weaker staining for the intra-cellular domain of E-cadherin (median 4 (IQR 0.5–6) and median 9 (IQR 9–12), for tumours with and without nuclear E-cadherin, respectively), and with a lower rate of re-intervention (p = 0.03). Conclusions Considering our results and the benign course of NF-PitNETs, we suggest that a high N-cadherin and downregulation of membranous E-cadherin are not associated with a more aggressive tumour behaviour in these subgroups of NF-PitNETs.

KLHL14 and E Cadherin Nuclear Co-expression as Predicting Factor of Nonfunctioning Pituitary Adenomas Invasiveness: Preliminary study

“…In literature, the aberrant nuclear expression E-Cad has been reported in different type of cancers and there are numerous evidences of its correlation with malignant transformation and/or metastatic process [40][41][42]. In agreement with our findings, nuclear accumulation of E-Cad has been recently documented also in NFPA and IPA [11,43].However, the present study represents the first report of an aberrant nuclear expression of E-Cad together with KLHL14 in NFPA, at the best of our knowledge. Finally, we here have documented a specific co-localization of KLHL14 and E-Cad signals in NFPA samples.…”

Aggressive PitNETs and Potential Target Therapies: A Systematic Review of Molecular and Genetic Pathways

“…Many authors described a loss of extracellular E-cadherin expression in PitNETs, and an intranuclear accumulation of E-cadherin was observed [29,185,186]. This was also true when E-cadherin expression was associated with PitNETs' clinical behavior: reduced extracellular and nuclear expression of E-cadherin was statistically associated with increased dimensions, invasion of adjacent structures, and a more aggressive behavior [187][188][189]. Some authors even showed these alterations to be of prognostic significance, as nuclear expression of E-cadherin was correlated with disease-free survival and a longer time to reintervention in clinically silent FSH/LH-PitNETs [190].…”