Endocrine Abstracts

Purpose: Clinically Non-Functioning Pituitary Neuroendocrine Tumours (NF-PitNETs) present a varying degree of aggressiveness, and reliable prognostic markers are lacking. We aimed to characterize the distribution of E- and N-cadherin in corticotroph, PIT1 and null-cell NF-PitNETs, and link it to the clinical course of the tumours.

Methods: We investigated the distribution of E- and N-cadherin by immunohistochemistry in a retrospective cohort of thirty tumours of the less common NF-PitNETs (corticotroph (n=18), PIT1 (n=8) and null-cell PitNETs (n=4)). Immunoreactive scores were compared to previously presented cohorts of gonadotroph NF-PitNETs and corticotroph functioning PitNETs.

Results: We found a low immunoreactive score (IRS) for the extracellular domain of E-cadherin, a medium to high IRS for the intracellular domain of E-cadherin and a high IRS for N-cadherin throughout the cohort. The corticotroph NF-PitNETs presented a higher IRS for the extracellular (median 0 (IQR 0-2) and the intracellular (median 9 (IQR 6-12) domain of E-cadherin, and a lower proportion of tumours presenting nuclear E-cadherin (17%) compared to the previous presented gonadotroph NF-PitNETs (P-value < 0.001 for all three comparisons). Presence of nuclear E-cadherin was associated with a weaker staining for the intracellular domain of E-cadherin by the cell membrane (median 4 (IQR 0.5-6) and 9 (IQR 9-12) for tumours with and without nuclear E-cadherin respectively, P-value <0.001). None of the eight patients presenting tumours with nuclear E-cadherin went through reintervention, while 9 out of 21 without nuclear E-cadherin went through reintervention (P-value 0.03).

Conclusion: The immunohistochemical staining for N-cadherin was high throughout the presented cohort. The IRS for E-cadherin varied between subtypes of NF-PitNETs. Nuclear E-cadherin was associated with a lower IRS of the intracellular domain of E-cadherin by the membrane, and with a low rate of reintervention. 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 an aggressive clinical course in NF-PitNETs.