The expression of neural cell adhesion molecule and the microenvironment of pituitary neuroendocrine tumours

Abstract

The neural cell adhesion molecule (NCAM) has previously been studied in pituitary neuroendocrine tumours (PitNETs), but its role in tumour biology and aggressiveness remains controversial, and its relationship with the tumour microenvironment remains unknown. We aimed to characterise NCAM expression in PitNETs, to correlate this with clinico-pathological features, and to assess the role of various microenvironment components on NCAM expression. NCAM and immune cells were investigated by immunohistochemistry in 16 human non-functioning-PitNETs (NF-PitNETs) and eight somatotrophinomas, including macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20), and neutrophils (neutrophil elastase). Five normal pituitaries were included for comparison. The cytokine secretome from these PitNETs and from PitNETderived tumour-associated fibroblasts (TAFs) were assessed on culture supernatants using a multiplex immunoassay panel. There were no significant NCAM expression differences between PitNETs and normal pituitary, and no difference between types of pituitary tumours (NF-PitNETs vs. somatotrophinomas). There was no association between NCAM expression and different clinico-pathological features, including cavernous sinus invasion and Ki-67, nor with serum hormone levels. NCAM immunoreactivity correlated negatively with PitNET-derived CXCL10 (rho = −0.417; p = .042) and CX3CL1 (rho = −0.423; p = .040) levels. NCAM immunoreactivity was negatively correlated with TAF-derived fibroblast growth factor (FGF)-2 (rho = −0.632; p = .009), but not with other TAF-derived cytokines. Within the PitNET cohort, there were no correlations between NCAM immunoreactivity and immune infiltrates or ratios, although, within NF-PitNETs, NCAM expression was higher in tumours with more FOXP3+ cells. NCAM expression does not differ between PitNETs and normal pituitary, and does not appear to relate to tumour invasiveness or proliferation.However, our data suggest a possible role for cytokines in the modulation of NCAM expression in PitNETs, particularly CXCL10, CX3CL1 and FGF-2, but not for immune cell infiltrates.

Prognostic Factors for Invasiveness and Recurrence of Pituitary Adenomas: A Series of 94 Patients

“…As a biomarker, CD-56 can be also expressed in normal neuroendocrine cells and neuroendocrine neoplasms, and thus, it is considered a potential neuroendocrine marker whereas the loss of its expression has been associated with increased metastatic risk, progression of malignant neoplasms such as myeloma, myeloid leukemia, pheochromocytoma, cholangiocarcinoma and paraganglioma [ 29 , 30 ]. Regarding adenohypophyseal cells, considered neuroendocrine cells expressing neuroendocrine proteins such as synaptophysin, chromogranin A and CD-56 [ 31 ], the existing data from the literature although limited have demonstrated that CD-56 expression does not differ between normal pituitary gland cells and PA cells [ 32 , 33 ]. Furthermore, CD-56 does not seem to be related to either PAs proliferation or its invasiveness [ 32 , 34 , 35 ].…”

“…Regarding adenohypophyseal cells, considered neuroendocrine cells expressing neuroendocrine proteins such as synaptophysin, chromogranin A and CD-56 [ 31 ], the existing data from the literature although limited have demonstrated that CD-56 expression does not differ between normal pituitary gland cells and PA cells [ 32 , 33 ]. Furthermore, CD-56 does not seem to be related to either PAs proliferation or its invasiveness [ 32 , 34 , 35 ]. Indeed, in our study CD-56 expression was not significantly correlated with any imaging characteristic of PA (size, extrasellar or cavernous sinus invasion) nor with recurrence.…”

VISTA is associated with immune infiltration and predicts favorable prognosis in TNBC

“…The antibodies used included anti-panCK, anti-HLA-DR and anti-CD68. Previous studies used CD68 and HLA-DR for M1 identification ( 22 – 25 ). Hence, in this study, CD68 and HLA-DR double-positive cells were defined as M1 macrophages.…”