Pituitary Tumors

Overview

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Messenger RNA
  • ADCYAP1
  • Multiple Endocrine Neoplasia Type 1
  • Oligonucleotide Array Sequence Analysis
  • Rats, Wistar
  • Statistics, Nonparametric
  • PTTG1
  • Cohort Studies
  • DNA Methylation
  • Securin
  • Childhood Cancer
  • Prolactinoma
  • Mutation
  • Neoplastic Cell Transformation
  • MicroRNAs
  • Genetic Predisposition
  • Biomarkers, Tumor
  • Immunohistochemistry
  • Epigenetics
  • Cancer Gene Expression Regulation
  • Restriction Mapping
  • Growth Hormone-Secreting Pituitary Adenoma
  • Case-Control Studies
  • Gene Expression
  • Pedigree
  • Pituitary Gland
  • Intracellular Signaling Peptides and Proteins
  • Adolescents
  • Germ-Line Mutation
  • Single Nucleotide Polymorphism
  • Receptors, CXCR
  • LRIG3
  • ACTH-Secreting Pituitary Adenoma
  • Gene Expression Profiling
  • Pituitary Tumors
  • Neoplasm Proteins
  • Acromegaly
  • DNA Mutational Analysis
  • ASH1L
  • GTP-Binding Protein alpha Subunits, Gs
  • Trans-Activators
  • NNAT
  • Proto-Oncogene Proteins c-kit
  • PLAGL1
  • Adenoma
  • Cell Proliferation
Tag cloud generated 10 March, 2017 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (29)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

GeneLocationAliasesNotesTopicPapers
POMC 2p23.3 LPH, MSH, NPP, POC, ACTH, CLIP -POMC and Pituitary Tumors
99
SSTR2 17q24 -SSTR2 and Pituitary Tumors
37
PRKAR1A 17q24.2 CAR, CNC, CNC1, PKR1, TSE1, ADOHR, PPNAD1, PRKAR1, ACRDYS1 -PRKAR1A and Pituitary Tumors
32
GHRH 20q11.2 GRF, INN, GHRF -GHRH and Pituitary Tumors
30
POU1F1 3p11 PIT1, CPHD1, GHF-1, Pit-1, POU1F1a -POU1F1 and Pituitary Tumors
20
SSTR5 16p13.3 SS-5-R -SSTR5 and Pituitary Tumors
17
MEG3 14q32 GTL2, FP504, prebp1, PRO0518, PRO2160, LINC00023, NCRNA00023, onco-lncRNA-83 -MEG3 and Pituitary Tumors
10
SSTR3 22q13.1 SS3R, SS3-R, SS-3-R, SSR-28 -SSTR3 and Pituitary Tumors
9
SSTR1 14q13 SS1R, SS1-R, SRIF-2, SS-1-R -SSTR1 and Pituitary Tumors
9
DRD2 11q23.2 D2R, D2DR -DRD2 and Pituitary Tumors
9
PYGM 11q13.1 -PYGM and Pituitary Tumors
8
NEUROD1 2q32 BETA2, BHF-1, MODY6, NEUROD, bHLHa3 -NEUROD1 and Pituitary Tumors
7
HMGA1 6p21 HMG-R, HMGIY, HMGA1A -HMGA1 and Pituitary Tumors
6
PLAGL1 6q24-q25 ZAC, LOT1, ZAC1 -PLAGL1 and Pituitary Tumors
5
DLK1 14q32 DLK, FA1, ZOG, pG2, DLK-1, PREF1, Delta1, Pref-1 -DLK1 and Pituitary Tumors
5
ADCYAP1 18p11 PACAP -PACAP expression in Prostate Cancer
5
PTTG1 5q35.1 EAP1, PTTG, HPTTG, TUTR1 -PTTG1 and Pituitary Tumors
4
POLK 5q13 DINP, POLQ, DINB1 -POLK and Pituitary Tumors
3
AVPR1A 12q14.2 V1aR, AVPR1, AVPR V1a -AVPR1A and Pituitary Tumors
3
PDE11A 2q31.2 PPNAD2 -PDE11A and Pituitary Tumors
3
NNAT 20q11.2-q12 Peg5 -NNAT and Pituitary Tumors
3
AVPR1B 1q32 AVPR3 -AVPR1B and Pituitary Tumors
3
CNTF 11q12.1 HCNTF -CNTF and Pituitary Tumors
2
LAPTM4B 8q22.1 LC27, LAPTM4beta -LAPTM4B and Pituitary Tumors
2
WNT4 1p36.23-p35.1 WNT-4, SERKAL -WNT4 and Pituitary Tumors
2
CHGA 14q32 CGA -CHGA and Pituitary Tumors
2
PITX1 5q31.1 BFT, CCF, POTX, PTX1, LBNBG -PITX1 and Pituitary Tumors
2
LRIG3 12q14.1 LIG3 -LRIG3 and Pituitary Tumors
1
ASH1L 1q22 ASH1, KMT2H, ASH1L1 -ASH1L and Pituitary Tumors
1

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

Glebauskiene B, Liutkeviciene R, Vilkeviciute A, et al.
Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development?
Dis Markers. 2017; 2017:5839528 [PubMed] Free Access to Full Article Related Publications
Purpose. To determine if the MMP-9 genotype has an influence on development of pituitary adenoma (PA). Methodology. The study enrolled n = 86 patients with PA and n = 526 healthy controls (reference group). The genotyping of MMP-9 was carried out using the real-time polymerase chain reaction method. Results. Our data demonstrated that the MMP-9 (-1562) C/C genotype was more frequent in PA group than in healthy controls (81.4% versus 64.6%, p = 0.002); C/C genotype was more frequently present in PA females compared to healthy control females, 81.5% versus 64.6%, p = 0.018, as well. MMP-9 (-1562) C/C genotype was frequently observed for all subgroups: noninvasive and invasive, nonrecurrence, and inactive PA compared to healthy controls: 81.8% versus 64.6%, p = 0.021; 81.0% versus 64.6%, p = 0.041; 81.8% versus 64.6%, p = 0.005; 100.0% versus 64.6%, p < 0.001, respectively. MMP-9 (-1562) C/C genotype was more frequent in inactive PA compared to active PA: 100.0% versus 71.4%; p < 0.001. Conclusion. MMP-9 (-1562) C/C genotype plays a role in nonrecurrence, inactive, and invasive as well as in nonivasive PA development.

Ritvonen E, Pitkänen E, Karppinen A, et al.
Impact of AIP and inhibitory G protein alpha 2 proteins on clinical features of sporadic GH-secreting pituitary adenomas.
Eur J Endocrinol. 2017; 176(2):243-252 [PubMed] Related Publications
INTRODUCTION: In sporadic acromegaly, downregulation of AIP protein of the adenomas associates with invasive tumor features and reduced responsiveness to somatostatin analogues. AIP is a regulator of Gai signaling, but it is not known how the biological function of the Gai pathway is controlled.
AIM: To study GNAS and AIP mutation status, AIP and Gai-2 protein expressions, Ki-67 proliferation indices and clinical parameters in patients having primary surgery because of acromegaly at a single center between years 2000 and 2010.
RESULTS: Sixty patients (F/M, 31/29), mean age 49 (median 50), mean follow-up 7.7 years (range 0.6-14.0) underwent primary surgery. Four adenoma specimens (6.8%) harbored an AIP and 21 (35.6%) an activating GNAS (Gsp+) mutation. Altogether 13/56 (23%) adenomas had low AIP protein levels, and 14/56 (25%) low Gai-2 staining. In regression modeling, AIP expression associated with Gai-2 (P = 2.33 × 10(-9)) and lower Ki-67 (P = 0.04). In pairwise comparison, low AIP protein predicted high GH at last follow-up (mean 7.7 years after surgery, q = 0.045). Extent of treatments given for acromegaly associated with higher preoperative GH (P = 7.94 × 10(-4)), KNOSP (P = 0.003) and preoperative hypopituitarism (P = 0.03) and remission at last follow-up with change in 3-month postoperative IGF1 (P = 2.07 × 10(-7)).
CONCLUSIONS: We demonstrate, for the first time, that AIP protein expression associates with Gai-2 protein intensities in sporadic somatotropinomas, suggesting a joint regulation on somatostatin signaling. Low AIP level associates with higher proliferative activity and predicts high GH concentrations after long-term follow-up. The AIP mutation rate of 6.8% is fairly high, reflecting the genetic composition of the Finnish population.

He W, Huang L, Shen X, et al.
Relationship between RSUME and HIF-1α/VEGF-A with invasion of pituitary adenoma.
Gene. 2017; 603:54-60 [PubMed] Related Publications
The RWD-containing sumoylation enhancer (RSUME) can stabilize hypoxia-inducible factor-1α (HIF-1α) which promotes vascular endothelial growth factor-A (VEGF-A) expression. RSUME plays an important role in promoting the invasion of pituitary adenoma. In this study, we compared the mRNA and protein levels of RSUME, HIF-1α, and VEGF-A in pituitary adenoma tissue and analyzed the correlation. We found that the expression levels of RSUME, HIF-1α, and VEGF-A in invasive pituitary adenoma were significantly higher than in noninvasive pituitary adenoma. Moreover, a positive correlation was found between RSUME and HIF-1α/VEGF pathways. RSUME and HIF-1α were treated with hypoxia-mimicking CoCl2 and transfected into AtT-20 and GT1.1 cell lines to determine the relationship between them. It was found that RSUME effects post-transcriptional expression of HIF-1α regulated VEGF-A secretion. Reducing RSUME expression using siRNA transfection resulted in a decrease of the invasion inhibition rate of AtT-20 cells, as determined using Transwell and MTT assays. Together, we found that RSUME silencing can inhibit the invasion of pituitary adenoma cells.

Robinson LC, Santagata S, Hankinson TC
Potential evolution of neurosurgical treatment paradigms for craniopharyngioma based on genomic and transcriptomic characteristics.
Neurosurg Focus. 2016; 41(6):E3 [PubMed] Related Publications
The recent genomic and transcriptomic characterization of human craniopharyngiomas has provided important insights into the pathogenesis of these tumors and supports that these tumor types are distinct entities. Critically, the insights provided by these data offer the potential for the introduction of novel therapies and surgical treatment paradigms for these tumors, which are associated with high morbidity rates and morbid conditions. Mutations in the CTNNB1 gene are primary drivers of adamantinomatous craniopharyngioma (ACP) and lead to the accumulation of β-catenin protein in a subset of the nuclei within the neoplastic epithelium of these tumors. Dysregulation of epidermal growth factor receptor (EGFR) and of sonic hedgehog (SHH) signaling in ACP suggest that paracrine oncogenic mechanisms may underlie ACP growth and implicate these signaling pathways as potential targets for therapeutic intervention using directed therapies. Recent work shows that ACP cells have primary cilia, further supporting the potential importance of SHH signaling in the pathogenesis of these tumors. While further preclinical data are needed, directed therapies could defer, or replace, the need for radiation therapy and/or allow for less aggressive surgical interventions. Furthermore, the prospect for reliable control of cystic disease without the need for surgery now exists. Studies of papillary craniopharyngioma (PCP) are more clinically advanced than those for ACP. The vast majority of PCPs harbor the BRAF(v600e) mutation. There are now 2 reports of patients with PCP that had dramatic therapeutic responses to targeted agents. Ongoing clinical and research studies promise to not only advance our understanding of these challenging tumors but to offer new approaches for patient management.

Martinez-Gutierrez JC, D'Andrea MR, Cahill DP, et al.
Diagnosis and management of craniopharyngiomas in the era of genomics and targeted therapy.
Neurosurg Focus. 2016; 41(6):E2 [PubMed] Related Publications
Craniopharyngiomas are rare intracranial neoplasms that pose clinical challenges due to their location adjacent to vital structures. The authors have previously shown high mutation rates of BRAF V600E in papillary craniopharyngioma and of CTNNB1 in adamantinomatous craniopharyngioma. These activating driver mutations are potential therapeutic targets, and the authors have recently reported a significant response to BRAF/MEK inhibition in a patient with multiply recurrent PCP. As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute-sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma. In this new era of genomic discovery, the treatment paradigm of craniopharyngioma is likely to change.

Apps JR, Martinez-Barbera JP
Molecular pathology of adamantinomatous craniopharyngioma: review and opportunities for practice.
Neurosurg Focus. 2016; 41(6):E4 [PubMed] Related Publications
Since the first identification of CTNNB1 mutations in adamantinomatous craniopharyngioma (ACP), much has been learned about the molecular pathways and processes that are disrupted in ACP pathogenesis. To date this understanding has not translated into tangible patient benefit. The recent development of novel techniques and a range of preclinical models now provides an opportunity to begin to support treatment decisions and develop new therapeutics based on molecular pathology. In this review the authors summarize many of the key findings and pathways implicated in ACP pathogenesis and discuss the challenges that need to be tackled to translate these basic science findings for the benefit of patients.

Yang Z, Zhang T, Gao H
Genetic aspects of pituitary carcinoma: A systematic review.
Medicine (Baltimore). 2016; 95(47):e5268 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs, the prognosis is poor and 66% of patients die within the first year. Existing therapeutic measures, including surgical removal, chemotherapy, and radiotherapy, have limited effectiveness. The lack of efficacy of current treatments is largely caused by the limited understanding of the molecular pathogenesis of PA and the malignant transformation to PC. Therefore, the aim of this systematic review was to summarize published research regarding gene and protein expression in PC to clarify the molecular mechanisms underlying PC genesis and development and identify new candidate diagnostic biomarkers and therapeutic targets for potential use in personalized treatment of PC.
METHODS: We followed the PRISMA guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of Science databases were searched for relevant studies conducted before December 16, 2015 describing the association of PC with gene expression at the mRNA and protein levels. MeSH terms combined with free terms were used to retrieve the references.
RESULTS: In total, 207 records were obtained by primary search, and 32 were included in the systematic review. Compared with normal pituitary gland and/or PA, 30 and 18 genes were found to have higher or lower expression, respectively, in PCs using different analytical methods. Among them, we selected 9 upregulated and 7 downregulated genes for further analysis based on their identification as candidate treatment targets in other cancers, potential clinical application, or further research value.
CONCLUSION: Previous studies demonstrated that many genes promote PC malignant transformation, angiogenesis, invasion, metastasis, and recurrence. Although most of these genes and proteins have not been fully analyzed with regard to their downstream mechanisms or potential diagnostic and therapeutic application, they have the potential to become candidate PC biomarkers and/or molecular targets for guiding personalized treatment. Modern advanced technologies should be utilized in future research to identify more candidate genes for PC pathogenesis, as precisely targeted gene therapies against PC are urgently required.

Matsumoto R, Izawa M, Fukuoka H, et al.
Genetic and clinical characteristics of Japanese patients with sporadic somatotropinoma.
Endocr J. 2016; 63(11):953-963 [PubMed] Related Publications
Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel gene mutations responsible for somatotropinoma have recently been reported. To determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed 61 consecutive Japanese patients with somatotropinoma without apparent family history. Comprehensive genetic analysis revealed that 31 patients harbored guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%) and three patients harbored aryl hydrocarbon receptor interacting protein (AIP) mutations (4.9%). No patients had G protein-coupled receptor 101 (GPR101) mutations. The patients in this cohort study were categorized into three groups of AIP, GNAS, and others and compared the clinical characteristics. The AIP group exhibited significantly younger age at diagnosis, larger tumor, and higher nadir GH during oral glucose tolerance test. In all patients with AIP mutation, macro- and invasive tumor was detected and repetitive surgery or postoperative medical therapy was needed. One case showed a refractory response to postoperative somatostatin analogue (SSA) but after the addition of cabergoline as combined therapy, serum IGF-I levels were controlled. The other case showed a modest response to SSA and the switching to cabergoline monotherapy was also effective. These data suggest that although resistance to SSA has been reported in patients with AIP mutations, the response to dopamine agonist (DA) may be retained. In conclusion, the cause of sporadic somatotropinoma in Japanese patients was comparable with the previous reports in Caucasians, patients with AIP mutations showed unique clinical characteristics, and DA may be a therapeutic option for patients with AIP mutations.

Zhou K, Zhang T, Fan Y, et al.
MicroRNA-106b promotes pituitary tumor cell proliferation and invasion through PI3K/AKT signaling pathway by targeting PTEN.
Tumour Biol. 2016; 37(10):13469-13477 [PubMed] Related Publications
The purpose of this study was to investigate the expression of microRNA-106b (miR-106b) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in pituitary tumor and to confirm whether miR-106b promotes proliferation and invasion of pituitary tumor cells through the PI3K/AKT signaling pathway by targeted regulation of PTEN expression, and thereby to find new targets for the treatment of pituitary tumor. Fifty-five cases of pituitary tumor tissue samples were collected, including 29 cases of invasive pituitary tumor, non-invasive 26 cases, and 8 normal pituitaries. The expression level of miR-106b in pituitary tumor tissue was detected by quantitative real-time PCR, and the expression of PTEN protein was detected by immunohistochemistry. PTEN 3'-untranslated region (UTR) luciferase vector was constructed, and dual-luciferase reporter gene assay was employed to examine the effect of miR-106b on PTEN 3'-UTR luciferase activity. AtT-20 cells were transfected with miR-106b mimics, miR-106b inhibitor, PTEN expression plasmid, and miR-106b mimics + PTEN expression plasmid respectively, and the changes in cellular proliferation and invasion were observed via MTT method and transwell assay respectively. PTEN messenger RNA (mRNA) expression was determined by quantitative real-time PCR, and western blotting was performed to detect the expression of PTEN, PI3K, AKT, and pAKT. miR-106b showed up-regulation in invasive pituitary tumor tissue: the expression level was significantly up-regulated compared with normal tissues and the non-invasive pituitary tumor tissue (P < 0.05). The positive rate of PTEN protein expression in invasive pituitary tumor tissues was significantly lower than in normal and non-invasive tissues (P < 0.01). Dual-luciferase reporter gene assay showed that miR-106b could bind to the 3'-UTR of PTEN specifically and significantly inhibited the luciferase activity, cutting the 46 % (P < 0.01). Down-regulation of miR-106b or up-regulation of PTEN could suppress cell proliferation and invasion of AtT-20 cells, and PTEN expression plasmid could partially simulate the function of miR-106b. Expression of PTEN mRNA and protein decreased significantly in AtT-20 cells overexpressing miR-106b. The expression levels of PI3K and p-AKT were significantly inhibited by miR-106b inhibitor and increased by miR-106b mimics. The expression of miR-106b showed up-regulation in pituitary tumor tissues, while the protein expression of PTEN presented opposite results. The findings of this study further demonstrated that miR-106b as an oncogene regulated the pituitary tumor cell proliferation and invasion in vitro by directly targeting PTEN through the PI3K/AKT signaling pathway. Our study suggests that miR-106b and PTEN are likely to serve as potential diagnostic biomarkers or therapeutic targets for pituitary tumor treatment in the future.

Liu HY, Gu WJ, Wang CZ, et al.
Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case-control trials.
Medicine (Baltimore). 2016; 95(24):e3904 [PubMed] Free Access to Full Article Related Publications
The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61-11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91-3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63-7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52-6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06-2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48-2.20, P = 0.95).The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.

Melo FM, Couto PP, Bale AE, et al.
Whole-exome identifies RXRG and TH germline variants in familial isolated prolactinoma.
Cancer Genet. 2016; 209(6):251-7 [PubMed] Related Publications
Familial isolated pituitary adenoma (FIPA) is a rare genetic disorder. In a subset of FIPA families AIP germline mutations have been reported, but in most FIPA cases the exact genetic defect remains unknown. The present study aimed to determine the genetic basis of FIPA in a Brazilian family. Three siblings presented with isolated prolactin genes. Further mutation screening was performed using whole-exome sequencing and all likely causative mutations were validated by Sanger sequencing. In silico analysis and secreting pituitary adenoma diagnosed through clinical, biochemical and imaging testing. Sanger sequencing was used to genotype candidate prolactinoma-mutated additional predictive algorithms were applied to prioritize likely pathogenic variants. No mutations in the coding and flanking intronic regions in the MEN1, AIP and PRLR genes were detected. Whole-exome sequencing of three affected siblings revealed novel, predicted damaging, heterozygous variants in three different genes: RXRG, REXO4 and TH. In conclusion, the RXRG and TH possibly pathogenic variants may be associated with isolated prolactinoma in the studied family. The possible contribution of these genes to additional FIPA families should be explored.

Wierzbicka-Tutka I, Sokołowski G, Bałdys-Waligórska A, et al.
PTTG and Ki-67 expression in pituitary adenomas.
Przegl Lek. 2016; 73(2):53-8 [PubMed] Related Publications
INTRODUCTION: The unpredictable biology of pituitary adenomas makes it a therapeutic challenge. Moreover ,histopathology of pituitary carcinomas and locally invasive adenomas are indistinguishable from benign tumors and a new marker which would enable to differentiate those lesions is vital. The aim of the study was to evaluate Ki-67 and PTTG (pituitary tumour--transforming gene) expression in pituitary adenomas and their applicationas markers of tumour aggressiveness.
MATERIAL AND METHODS: A retrospective analysis of 55 patients: 32 females(58%) and 23 males (42%), mean age 50 ± 16 years who underwent pituitary tumor surgery between 2003-2012. Ki-67 and PTTG indices were determined by immunohistochemical staining. Magnetic resonance imaging or computed tomography was performed beforehand and one year after surgery to figure a potential tumour progression, tumour size and correlation to adjacent tissues.
RESULTS: The expression of Ki-67and PTTG was revealed in cell nucleiin 88% and 85% of adenomas, respectively. The median Ki-67 and PTTG indices were 1.4 and 1.0, respectively(p = 0.006). In the group with macroadenoma as compared with the group with microadenoma, median Ki-67 index was higher (1.4% vs. 1.03%; p = 0.02). We did not find correlation between both Ki-67 and PTTG indices and tumour progression. Tumours with positive immunostaining towards FSH revealed lower Ki-67 and PTTG indices than the rest with a negative one (0.6% vs.1.84%, p = 0.0004 and 0.67% vs 1.23%,p = 0.047; respectively). However, PTTG index was higher in the group with acromegaly as compared to the group with clinically non-functioning pituitary adenoma (NFPA) (1.28% vs.0.35%; p = 0.02).
CONCLUSIONS: Positive nuclear expression of Ki-67 and PTTG was observed in the majority of pituitary adenomas. Only higher Ki-67 expression was related to the tumour invasiveness found on MRI/CT. Tumour progressionwas not related to both Ki-67 and PTTG expression.

Peculis R, Balcere I, Rovite V, et al.
Polymorphisms in MEN1 and DRD2 genes are associated with the occurrence and characteristics of pituitary adenomas.
Eur J Endocrinol. 2016; 175(2):145-53 [PubMed] Related Publications
OBJECTIVE: Although pituitary adenomas (PAs) affect a significant proportion of the population, only a fraction have the potential to become clinically relevant during an individual's lifetime, causing hormonal imbalance or complications due to mass effect. The overwhelming majority of cases are sporadic and without a clear familial history, and the genotype-phenotype correlation in PA patients is poorly understood. Our aim was to investigate the involvement of genes known for their role in familial cases on drug response and tumor suppression in the development and pathology of PAs in a patient group from Latvia.
DESIGN: The study included 143 cases and 354 controls, we investigated the role of single-nucleotide polymorphisms (SNPs) in seven genes (SSTR2, SSTR5, DRD2, MEN1, AIP, GNAS, and PRKAR1A) associated with pituitary tumor occurrence, phenotype, and clinical symptoms.
METHODS: Genotyping of 96 tag and nonsynonymous SNPs was performed in the genomic regions of interest.
RESULTS: We discovered a significant association (OR=17.8, CI 0.95=2.18-145.5, P=0.0002) between a rare MEN1 mutation (rs2959656) and clinically active adenoma in our patients. Additionally, rs7131056 at DRD2 was associated with a higher occurrence of extrasellar growth in patients with prolactinoma and somatotropinoma (OR=2.79, CI 0.95=1.58-4.95, P=0.0004).
CONCLUSIONS: rs2959656, a nonsynonymous variant in MEN1, is associated with the development of clinically active PA. Furthermore, rs7131056 in DRD2 contributes to either faster growth of the adenoma or reduced symptomatic presentation, allowing PAs to become larger before detection.

Wang DS, Zhang HQ, Zhang B, et al.
miR-133 inhibits pituitary tumor cell migration and invasion via down-regulating FOXC1 expression.
Genet Mol Res. 2016; 15(1) [PubMed] Related Publications
Many studies have shown that microRNA (miR)-133 functions as a tumor suppressor in a variety of metastatic cancers, including breast cancer, gastric cancer, and liver fibrosis. However, the influence of miR-133 on pituitary tumor malignancy has not yet been reported. The purpose of this study was to explore the role of miR-133 in pituitary tumor cell migration and invasive ability and the molecular mechanisms involved. Our findings suggest that in pituitary adenoma cell lines, through direct targeting and negative control of forkhead box C1 (FOXC1), miR-133 can inhibit pituitary adenoma cell migration and invasion. In addition, epithelial-to-mesenchymal transition can be induced by miR-133. Additionally, a negative correlation was found between FOXC1 and miR-133 expression when comparing their expression levels between cancerous tissue and adjacent normal tissue. This suggests that miR-133 can inhibit cell migration and invasion by directly targeting FOXC1, implying that miR-133 could be a potential therapeutic target for treatment of invasive pituitary adenoma.

Tabuchi Y, Kitamura T, Fukuhara A, et al.
Nur77 gene expression levels were involved in different ACTH-secretion autonomy between Cushing's disease and subclinical Cushing's disease.
Endocr J. 2016; 63(6):545-54 [PubMed] Related Publications
Cushing's disease (CD) and subclinical Cushing's disease (subCD) are both diseases caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. However, ACTH autonomy in subCD is weaker than in CD and there are no Cushingoid features in subCD. The differences of molecular mechanisms in ACTH autonomy between CD and subCD have not yet been reported. Therefore, we aimed to investigate the differences in molecular mechanisms of ACTH-secretion autonomy between CD and subCD. The study included 23 patients [7 CD, 6 subCD, and 10 non-functioning pituitary tumors (NFTs)] who underwent transsphenoidal surgery at the Osaka University Hospital between December 2009 and October 2013. Using quantitative real-time PCR, various ACTH-related gene expressions in tumor tissues from CD, subCD, and NFT were measured such as pro-opiomelanocortin (POMC), POMC transcription factor (Tpit, Pitx1, NeuroD1, and Nur77), POMC peptide processing enzymes (prohormone convertase: PC1/3 and PC2), and ACTH secretion-related factors (corticotropin-releasing hormone receptor 1: CRHR1 and glucocorticoid receptor α: GRα). Only Nur77 mRNA levels were significantly higher in CD than in subCD. Furthermore, we stained 6 CD and 6 subCD with anti-Nur77 antibody. All tumor samples from CD had Nur77 protein positive cells. On the other hand, Nur77 protein was expressed in only one tumor sample from subCD. This sample showed high expression of Nur77 mRNA. Nur77 is an important to regulate POMC transcription and negative-feedback by glucocorticoids. Nur77 gene expression levels might involve different autonomy of ACTH production between CD and subCD.

Gradiser M, Matovinovic Osvatic M, Dilber D, Bilic-Curcic I
Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.
Int J Environ Res Public Health. 2016; 13(3) [PubMed] Free Access to Full Article Related Publications
The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

Hölsken A, Sill M, Merkle J, et al.
Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles.
Acta Neuropathol Commun. 2016; 4:20 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Craniopharyngiomas (CP) are rare epithelial tumors of the sellar region. Two subtypes, adamantinomatous (adaCP) and papillary CP (papCP), were previously identified based on histomorphological and epidemiological aspects. Recent data indicates that both variants are defined by specific genetic alterations, and influenced by distinct molecular pathways and particular origins. The fact that CP is an uncommon tumor entity renders studies on large cohorts difficult and exceptional. In order to achieve further insights distinguishing CP variants, we conducted whole genome methylation (450 k array) and microarray-based gene expression studies in addition to CTNNB1 and BRAF mutation analysis using a comprehensive cohort of 80 adaCP and 35 papCP.
RESULTS: BRAF V600E mutations were solely found in the papCP subgroup and were not detectable in adaCP samples. In contrast, CTNNB1 mutations were exclusively detected in adaCP. The methylome fingerprints assigned DNA specimens to entity-specific groups (papCP (n = 18); adaCP (n = 25)) matching perfectly with histology-based diagnosis, suggesting that they represent truly distinct biological entities. However, we were not able to detect within the adaCP group (including 11 pediatric and 14 adult cases) a significant difference in methylation signature by age. Integrative comparison of the papCP with the adaCP group based on differential gene expression and methylation revealed a distinct upregulation of Wnt- and SHH signaling pathway genes in adaCP.
CONCLUSIONS: AdaCP and papCP thus represent distinct tumor subtypes that harbor mutually exclusive gene mutations and methylation patterns, further reflected in differences in gene expression. This study demonstrates that DNA methylation analyses are an additional method to classify CP into subtypes, and implicates a role of epigenetic mechanisms in the genesis of the respective CP variants. Detection of tumor-specific signaling pathway activation enables the possibility of target-oriented intervention.

Saeger W, Petersenn S, Schöfl C, et al.
Emerging Histopathological and Genetic Parameters of Pituitary Adenomas: Clinical Impact and Recommendation for Future WHO Classification.
Endocr Pathol. 2016; 27(2):115-22 [PubMed] Related Publications
The review assesses immunohistochemical findings of somatostatin receptors and of metalloproteinases in different pituitary adenoma types and the significance of molecular genetic data. Current evidence does not support routine immunohistochemical assessment of somatostatin or dopamine receptor subtype expression on hormone-secreting or nonfunctioning pituitary adenomas. Further prospective studies are needed to define its role for clinical decision making. Until then we suggest to restrict membrane receptor profiling to individual cases or for study purposes. The problems of adenoma expansion and invasion are discussed. Despite partially contradictory publications, proteases clearly play a major role in permission of infiltrative growth of pituitary adenomas. Therefore, detection of at least MMP-2, MMP-9, TIMP-2, and uPA seems to be justified. Molecular characterization is important for familial adenomas, adenomas in MEN, Carney complex, and McCune-Albright syndrome and can gain insight into pathogenesis of sporadic adenomas.

Gao F, Pan S, Liu B, Zhang H
TFF3 knockout in human pituitary adenoma cell HP75 facilitates cell apoptosis via mitochondrial pathway.
Int J Clin Exp Pathol. 2015; 8(11):14568-73 [PubMed] Free Access to Full Article Related Publications
Trefoil factor 3 (TFF3), a regulatory protein composed of 59 amino acids, has been suggested to be involved in pathogenesis, proliferation, differentiation, invasion, migration and apoptosis in multiple malignant tumors. This study thus investigated the effect of TFF3 knockout in human pituitary adenoma cell line HP75 on cell apoptosis and related pathways. RNA interference approach was used to knock down the expression of TFF3 protein. The gene silencing was validated by RNA denaturing gel electrophoresis and Western blotting. The effect of TFF3 knockout on cell apoptosis was analyzed by Western blotting and flow cytometry. TFF3 protein level in pituitary adenoma was about 3.61 ± 0.48 folds of that in normal tissues (P < 0.01). After transfecting with small interference RNA (siRNA) against TFF3, the apoptotic ration was significantly elevated (P < 0.01). Apoptosis related protein Bcl-2 and caspase-3 levels were remarkably depressed after siRNA transfection, while Bax and cleaved caspase-3 levels were elevated. TFF3 protein knockout can facilitate apoptosis of human pituitary adenoma HP75 cells via mitochondrial pathway.

Maggioli C, Cambiaso P, Ciccone S, et al.
Long-term first line medical treatment in a 4-year-old girl with Xq26.3 microduplication-negative somatotropinoma. Case report and literature review.
J Pediatr Endocrinol Metab. 2016; 29(4):497-501 [PubMed] Related Publications
Growth hormone (GH) secreting adenoma represents a therapeutic challenge in childhood. Because of its rarity no treatment guidelines are available and pediatric management often results from recommendations issued for adults. We report a case of a 4-year-old girl with somatotropinoma successfully treated with only medical treatment. She presented with tall stature and history of growth acceleration. Imaging and laboratory confirmed the diagnosis of GH secreting macroadenoma. She started medical treatment with a somatostatin analogue and a dopamine agonist. During an 8-year follow-up period, a good clinical control of the disease and a shrinkage of the adenoma have been demonstrated. At the last observation she achieved normal near-adult height and pubertal development. According to our experience and limited literature evidences, first line treatment with somatostatin analogues can be attempted in patients with somatotropinoma. This approach seems to be able to control the clinical course of the disease, allowing to postpone transphenoidal surgery to adult age or to avoid it.

Lecoq AL, Bouligand J, Hage M, et al.
Very low frequency of germline GPR101 genetic variation and no biallelic defects with AIP in a large cohort of patients with sporadic pituitary adenomas.
Eur J Endocrinol. 2016; 174(4):523-30 [PubMed] Related Publications
CONTEXT: Recently, germline and somatic GPR101 p.(E308D) mutation was found in patients with isolated acromegaly. It is not known whether GPR101 point mutations are associated with other histological types of pituitary adenoma.
OBJECTIVE: We sought germline GPR101 mutations in patients with sporadic pituitary adenomas, and compared the phenotypes of GPR101 mutation carriers and AIP mutation carriers.
DESIGN: An observational cohort study performed between 2007 and 2014 in a single referral center.
PARTICIPANTS: This prospective study involved 766 unselected patients (413 women) with sporadic pituitary adenomas of all histotypes.
METHODS: Entire GPR101 and AIP coding sequence were screened for germline mutations.
RESULTS: Twelve patients (1.6%) were found to carry the GPR101 p.(E308D) mutation or rare GPR101 variants. The minor allele frequency of the GPR101 mutation and variants was higher in patients with pituitary adenomas than in unaffected individuals included in the Exome Aggregation Consortium database. Three of the six patients with the GPR101 p.(E308D) mutation had adult-onset acromegaly, two had adrenocorticotropin-secreting adenomas, and one had a nonfunctioning macroadenoma. Six patients carried rare GPR101 variants. Germline AIP mutations or rare AIP variants were identified in 32 patients (4.2%). AIP mutation carriers were younger at diagnosis than GPR101 mutation carriers and non carriers. None of the patients harbored mutations in both the GPR101 and AIP genes.
CONCLUSION: Germline GPR101 mutations are very rare in patients with sporadic pituitary adenomas of various histotypes. No digenism with AIP was identified. Further studies are required to establish whether and how genetic variation in GPR101 gene contributes to pituitary tumorigenesis.

Zhou W, Ma CX, Xing YZ, Yan ZY
Identification of candidate target genes of pituitary adenomas based on the DNA microarray.
Mol Med Rep. 2016; 13(3):2182-6 [PubMed] Related Publications
The present study aimed to explore molecular mechanisms involved in pituitary adenomas (PAs) and to discover target genes for their treatment. The gene expression profile GSE4488 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the Limma package and analyzed by two‑dimensional hierarchical clustering. Gene ontology (GO) and pathway enrichment analyses were performed in order to investigate the functions of DEGs. Subsequently, the protein‑protein interaction (PPI) network was constructed using Cytoscape software. DEGs were then mapped to the connectivity map database to identify molecular agents associated with the underlying mechanisms of PAs. A total of 340 upregulated and 49 downregulated DEGs in PA samples compared with those in normal controls were identified. Hierarchical clustering analysis showed that DEGs were highly differentially expressed, indicating their aptness for distinguishing PA samples from normal controls. Significant gene ontology terms were positive regulation of immune system-associated processes for downregulated DEGs and skeletal system development for upregulated DEGs. Pathways significantly enriched by DEGs included extracellular matrix (ECM)‑receptor interaction, the Hedgehog (Hh) signaling pathway and neuroactive ligand‑receptor interaction. The PPI network was constructed with 117 nodes, 123 edges and CD44 and Gli2 as hub nodes. Furthermore, depudecin, a small molecule drug, was identified to be mechanistically associated with PA. The genes CD44 and Gli2 have important roles in the progression of PAs via ECM‑receptor interaction and the Hh signaling pathway and are therefore potential target genes of PA. In addition, depudecin may be a candidate drug for the treatment of PAs.

Yu SY, Hong LC, Feng J, et al.
Integrative proteomics and transcriptomics identify novel invasive-related biomarkers of non-functioning pituitary adenomas.
Tumour Biol. 2016; 37(7):8923-30 [PubMed] Related Publications
Non-functioning pituitary adenomas (NFPAs) are usually macroadenomas and display invasion into surrounding tissues. The treatment for invasive NFPAs is still challenging. This study describes the differential patterns of gene expression between invasive and non-invasive NFPAs and identifies novel biomarkers involved in invasion of NFPAs for diagnosis and treatment. Using gene microarray technology, we examined the gene expression profile and found 1160 differentially expressed messenger RNA (mRNA) between invasive and non-invasive NFPAs. Then, we examined the protein profile by liquid chromatography tandem mass spectrometry (LC-MS/MS) and found 433 differentially expressed proteins between invasive and non-invasive NFPAs. Subsequently, we integrated the proteomics and transcriptomics datasets and identified 29 common changed molecules. Through bioinformatics analysis using Ingenuity Pathway Analysis (IPA) software, we showed that the 29 molecules were enriched in 25 canonical signaling pathways, 25 molecular and cellular functions, and 2 networks. Eight genes were identified involved in the invasion function by the molecular and cellular functions analysis, including CAT, CLU, CHGA, EZR, KRT8, LIMA1, SH3GLB2 and SLC2A1. Furthermore, we validated the decreased CHGA expression and increased CLU expression in invasive NFPAs by qRT-PCR and Western blot. Our study demonstrated that integration of proteomics and transcriptomics could prove advantageous for accelerating tumor biomarker discovery and CHGA and CLU might be important novel biomarkers and therapeutic targets for invasion of NFPAs.

Miettinen M
[Succinate dehydrogenase-deficient tumors--a novel mechanism of tumor formation].
Duodecim. 2015; 131(22):2149-56 [PubMed] Related Publications
Succinate dehydrogenase (SDH) is a heterotetrameric enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation. These tumors, discovered during the past 15 years, often occur in young patients and include 15% of paragangliomas, 7% of gastric gastrointestinal stromal tumors (GISTs), and <1% of renal cell carcinomas and pituitary adenomas. SDH-deficient tumors have lost SDH complex activity via bi-allelic genomic losses or epigenetic silencing. This deficiency is oncogenic, activating pseudohypoxia signaling. SDH deficiency has to be suspected in the above-cited tumor types presenting at a young age. Immunohistochemical testing of tumor tissue for SDHB loss is diagnostic.

Gérard C, Jedidi H, Petrossians P, et al.
[Old phenotype and new genotypes. Pituitary adenomas].
Rev Med Liege. 2015; 70(11):569-74 [PubMed] Related Publications
Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

Sapochnik M, Nieto LE, Fuertes M, Arzt E
Molecular Mechanisms Underlying Pituitary Pathogenesis.
Biochem Genet. 2016; 54(2):107-19 [PubMed] Related Publications
During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

Zhang QJ, Xu C
The role of microRNAs in the pathogenesis of pituitary tumors.
Front Biosci (Landmark Ed). 2016; 21:1-7 [PubMed] Related Publications
Pituitary tumors, the most common intracranial tumors, lead to serious morbidity through the inappropriate secretion of pituitary hormones. The anomalous expression of microRNAs (miRNAs), which have a crucial status in the development and function of pituitary gland, promotes the tumorigenesis of hypothalamic-pituitary axis-related pituitary tumors. This mainly leads to alterations in the function of the hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and hypothalamic-pituitary-growth hormone. In the tumorigenesis of pituitary tumors, miRNAs have complex roles. They can induce cell cycle arrest, inhibiting cell proliferation and inducing apoptosis via different pathways; however, they also promote the occurrence of pituitary tumors through direct interactions with transcription factors. This review summarizes recent progress in the study of miRNAs on the pathogenesis of pituitary tumors.

Bujko M, Kober P, Zbijewska J, et al.
Microsatellite instability analysis in pituitary adenomas.
Neuro Endocrinol Lett. 2015; 36(5):511-4 [PubMed] Related Publications
OBJECTIVE: Mutator phenotypes with microsatellite instability (MSI) are observed in a subset of solid tumors including those localized in the brain. MSI arises from impaired DNA mismatch repair. It can be a potential marker of resistance to radiation and chemotherapy, as demonstrated for several cancer types. Our study aims are to investigate MSI incidence in pituitary adenomas (PA) with a currently recommended methodology.
METHODS: DNA was obtained from 107 patients with PA of which 83 adenomas were nonfunctioning, 13 somatotrophic, 9 lactotrophic and 2 corticotrophic. These were examined for MSI status by PCR and capillary electrophoresis using five quasimonomorphic microsatellite markers: BAT25, BAT26, NR21, NR24 and NR27; in accordance to current Bethesda guidelines.
RESULTS AND CONCLUSION: No microsatellite instability was detected in the tumor samples thus implying the lack of any clinical usefulness of MSI testing in PA cases.

Ronchi CL, Peverelli E, Herterich S, et al.
Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas.
Eur J Endocrinol. 2016; 174(3):363-72 [PubMed] Related Publications
CONTEXT: Alterations in the cAMP signaling pathway are common in hormonally active endocrine tumors. Somatic mutations at GNAS are causative in 30-40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical adenomas respectively. However, the pathogenesis of many GH-secreting adenomas remains unclear.
AIM: Comprehensive genetic characterization of sporadic GH-secreting adenomas and identification of new driver mutations.
DESIGN: Screening for somatic mutations was performed in 67 GH-secreting adenomas by targeted sequencing for GNAS, PRKACA, and USP8 mutations (n=31) and next-generation exome sequencing (n=36).
RESULTS: By targeted sequencing, known activating mutations in GNAS were detected in five cases (16.1%), while no somatic mutations were observed in both PRKACA and USP8. Whole-exome sequencing identified 132 protein-altering somatic mutations in 31/36 tumors with a median of three mutations per sample (range: 1-13). The only recurrent mutations have been observed in GNAS (31.4% of cases). However, seven genes involved in cAMP signaling pathway were affected in 14 of 36 samples and eight samples harbored variants in genes involved in the calcium signaling or metabolism. At the enrichment analysis, several altered genes resulted to be associated with developmental processes. No significant correlation between genetic alterations and the clinical data was observed.
CONCLUSION: This study provides a comprehensive analysis of somatic mutations in a large series of GH-secreting adenomas. No novel recurrent genetic alterations have been observed, but the data suggest that beside cAMP pathway, calcium signaling might be involved in the pathogenesis of these tumors.

Jia R, Li M, Chang B, et al.
Expression of Neuropeptide Y and Its Relationship with Molecular and Morphological Changes in Human Pituitary Adenomas.
Cancer Biother Radiopharm. 2015; 30(10):411-9 [PubMed] Related Publications
The purpose of this study was to explore the role of neuropeptide Y (NPY) on molecular and histological changes in human pituitary adenomas. The localization of NPY and its expression at the protein, messenger RNA (mRNA), and receptor levels were investigated here in different subcategories of pituitary adenomas. Immunohistochemical staining was performed in all cases to assess expression of NPY. Reverse transcription-polymerase chain reaction (RT-PCR) was used to study the mRNA expression of NPY. NPY subcellular localization was observed using immunoelectron microscopy in cytoplasm, rough endoplasmic reticulum, and cell matrix in four of the six cases of pituitary adenoma. NPY protein expression was observed in 59.6% of 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. mRNA expression of NPY was observed in all 57 cases of pituitary adenoma and in 2 cases of pituitary hyperplasia. Significantly different levels of expression were observed across different subcategories of pituitary adenoma. mRNA expression of Y1R and Y2R was observed across all subcategories of pituitary adenomas, and a positive correlation was observed between NPY and Y2R. In conclusion, evidence is provided here for the expression of NPY and its receptors, Y1R and Y2R, in human pituitary adenoma, and the levels of expression were found to differ across different subcategories. Differences in expression of Y2R in human pituitary adenomas were found to have remarkable statistical significance.

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