Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas

Ongaratti, Bárbara Roberta; Haag, Taiana; D’Ávila, Marícia Fantinel; Trott, Geraldine; Ferreira, Nelson Pires; Rech, Carolina Garcia Soares Leães; Pereira-Lima, Júlia Fernanda Semmelmman; Oliveira, Miriam da Costa

doi:10.1016/j.anndiagpath.2018.10.003

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…Nevertheless, it is important to note that most of these studies were performed in functioning pituitary tumors. Actually, in the case of NFPTs, we found no association between E-cadherin accumulation and invasion, results that are in agreement with two previous studies [44,45]. Another study found lower E-cadherin levels in invasive NFPTs [41].…”

Section: Discussionsupporting

confidence: 92%

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features

Flores-Martinez

Dios

Remón

et al. 2020

JCM

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The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST1-5 expression was also evaluated by immunohistochemistry. SST3 was the predominant SST subtype detected, followed by SST2, SST5, and SST1. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST2 and SST5. No major association between SSTs and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs.

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Section: Discussionsupporting

confidence: 92%

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features

Flores-Martinez

Dios

Remón

et al. 2020

JCM

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“…12 There were no associations with clinicopathological features, such as cavernous sinus invasion (p = .151), a feature regarded as a prognostic factor for recurrence and poorer outcomes in patients with PitNETs. 35,37 Our data therefore correspond with some previous similar findings, 27,30,38 as opposed to other studies that had reported higher expression of NCAM in association with invasive PitNETs. 13,29 This is in contrast to other types of tumours, where increased NCAM expression has been associated…”

Section: Discussionsupporting

confidence: 92%

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

Marques

Barry

Carlsen³

et al. 2021

J Neuroendocrinology

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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.

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“…With the purpose of developing diagnostic and therapeutic strategies, several biomarkers and pathways have been reported associated with invasiveness in NFPAs through gene expression data analysis. Some of the most momentous potential biomarkers related to the aggressive nature of NFPAs are pituitary tumor transforming gene 1 (PTTG1) 9 , Ezrin (EZR) 10 , Ectoderm-Neural Cortex 1 (ENC1) 11 , WNT Inhibitory Factor 1(WIF1) 12 , E-cadherin (CDH1) and Neural cell adhesion molecule (NCAM) 13 . Moreover, previous studies identified a perturbation in some signaling pathways that can make NFPAs prone to invasiveness.…”

Section: Introductionmentioning

confidence: 99%

Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness

Khayer

Jalessi

Jahanbakhshi

et al. 2021

Sci Rep

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Non-functioning pituitary adenomas (NFPAs) are typical pituitary macroadenomas in adults associated with increased mortality and morbidity. Although pituitary adenomas are commonly considered slow-growing benign brain tumors, numerous of them possess an invasive nature. Such tumors destroy sella turcica and invade the adjacent tissues such as the cavernous sinus and sphenoid sinus. In these cases, the most critical obstacle for complete surgical removal is the high risk of damaging adjacent vital structures. Therefore, the development of novel therapeutic strategies for either early diagnosis through biomarkers or medical therapies to reduce the recurrence rate of NFPAs is imperative. Identification of gene interactions has paved the way for decoding complex molecular mechanisms, including disease-related pathways, and identifying the most momentous genes involved in a specific disease. Currently, our knowledge of the invasion of the pituitary adenoma at the molecular level is not sufficient. The current study aimed to identify critical biomarkers and biological pathways associated with invasiveness in the NFPAs using a three-way interaction model for the first time. In the current study, the Liquid association method was applied to capture the statistically significant triplets involved in NFPAs invasiveness. Subsequently, Random Forest analysis was applied to select the most important switch genes. Finally, gene set enrichment (GSE) and gene regulatory network (GRN) analyses were applied to trace the biological relevance of the statistically significant triplets. The results of this study suggest that “mRNA processing” and “spindle organization” biological processes are important in NFAPs invasiveness. Specifically, our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.

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Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas

Cited by 7 publications

References 22 publications

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features

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

Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness

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