Brigita Glebauskiene

Role of MMP-2 (-1306 C/T) Polymorphism in Pituitary Adenoma

Purpose. To determine if the frequency of the genotype of MMP-2 (-1306 C/T) Rs243865 has an influence on the development of pituitary adenoma (PA). Methods. The study enrolled n = 84 patients with PA and a random sample of the population n = 318 (reference group). The genotyping test of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method. Results. Analysis of MMP-2 (-1306 C/T) gene polymorphism has not revealed any differences in the genotype (C/C, C/T, and T/T) distribution between the PA patients and the reference group (as follows: 50%, 44%, and 6% versus 59.75%, 33.96%, and 6.29%). MMP-2 (-1306) C/C genotype was rarely observed in noninvasive PA compared to healthy controls: 35.1% versus 59.75%; p = 0.0049, as well C/C genotype being more frequently detected in nonrecurrence PA compared to healthy controls: 46.5% versus 59.75%; p = 0.0468. MMP-2 (-1306) C/T genotype was more frequently present in PA females compared to healthy controls females: 49.1% versus 33.66%; p = 0.041. Conclusion. Patients with noninvasive and nonrecurrence pituitary adenoma were the carriers of the C/C genotype significantly more frequently than their control counterparts and the C/T genotype in females was more frequent.

N-myc downstream-regulated gene 2 ( NDRG2 ) promoter methylation and expression in pituitary adenoma

BackgroundPituitary adenoma (PA) is a benign primary tumor that arises from the pituitary gland and is associated with ophthalmological, neurological and endocrinological abnormalities. However, causes that increase tumor progressing recurrence and invasiveness are still undetermined. Several studies have shown N-myc downstream regulated gene 2 (NDRG2) as a tumor suppressor gene, but the role of NDRG2 gene in pituitary adenoma pathogenesis has not been elucidated. The aim of our research has been to examine NDRG2 mRNA expression in PA and to determine the associations between the NDRG2 gene epigenetic changes and the development of recurrence or invasiveness of PA and patient clinical data.MethodsThe MS-PCR was used for NDRG2 promoter methylation analysis and gene mRNA expression levels were evaluated by qRT-PCR in 68 non-functioning and 73 functioning adenomas. Invasiveness was evaluated using magnetic resonance imaging with Hardy’s modified criteria. Statistical analysis was performed to find correlations between NDRG2 gene mRNA expression, promoter methylation and patient clinical characteristics and PA activity.ResultsThe NDRG2 mRNA expression was significantly lower in the case of acromegaly (GH and IGF-1 hypersecretion) than in other diagnoses of PAs (p < 0.05). Also, the NDRG2 expression was significantly higher in prolactinoma (PRL hypersecretion) than in in other diagnoses of PAs (p < 0.05). The promoter of NDRG2 was methylated in 22.69% (12/58 functioning and 15/61 non-functioning) of patients with PA. However, the NDRG2 gene mRNA expression was not significantly related to its methylation status. Clinical factors, such as: age, gender, relapse and diagnoses of Cushing syndrome were of no significance for NDRG2 promoter methylation and mRNA expression levels, as well as secreting or non-secreting PAs and the invasiveness of PAs.ConclusionThe different NDRG2 promoter methylation and expression levels in PA samples showed tumor heterogeneity and indicates a potential role of this gene in pituitary adenoma pathogenesis, but the corresponding details require intensive research.

Association of Optic Neuritis with CYP4F2 Gene Single Nucleotide Polymorphism and IL-17A Concentration

Background The aetiology and pathophysiology of optic neuritis (ON) is not absolutely clear but genetic and inflammatory factors may be also involved in its development. The aim of the present study was to determine the influence of single nucleotide polymorphism (SNP) of CYP4F2 (rs1558139) and serum levels of IL-17A on ON development. Materials and Methods Forty patients with ON and 164 control subjects were evaluated. Patients were divided by gender, also ON patients were divided into two subgroups: ON with and without multiple sclerosis (MS). CYP4F2 rs1558139 was genotyped using real-time PCR. Serum IL-17A levels were measured using ELISA IL-17A kits. Results We found that A/A genotype of CYP4F2 rs1558139 was statistically significantly more frequent in men with ON and MS than in women: 57.1% versus 0%, p = 0.009. Also, allele A was statistically significantly more frequent in men with ON and MS than in women: 71.4% versus 37.5%, p = 0.044. Serum levels of IL-17A were higher in ON group than in control group: (median, IQR): 20.55 pg/ml, 30.66 pg/ml versus 8.97 pg/ml, 6.24 pg/ml, p < 0.001. Conclusion The higher IL-17A levels were found to be associated with ON, while allele A at rs1558139 was associated only with ON with MS in male patients.

Association of retinal nerve fibre layer thickness with quantitative magnetic resonance imaging data of the optic chiasm in pituitary adenoma patients

To evaluate retinal nerve fibre layer (RNFL) thickness in patients with pituitary adenoma (PA) by optical coherence tomography and to compare it with magnetic resonance imaging (MRI) characteristics of pituitary extension. 154 eyes of 77 patients with PA were evaluated. Ophthalmologic evaluation was performed before surgical treatment. Average and per quadrant thickness of peripapillary RNFL (internal limiting membrane to nerve fiber layer/ganglion cell layer) were calculated. Optical coherence tomography was performed in a disc circle mode (layer distance 3.45 mm; 1024 scans). PA was confirmed by MRI scans. Characteristics of the optic chiasm in relation to the suprasellar adenoma were assessed. Suprasellar extension of PA was diagnosed in 55 patients (71.4%). The optic chiasm thickness differed significantly in the groups with and without suprasellar PA extension (p < .001). A weak positive correlation was found between the height of the optic chiasm right side, middle part, left side and visual acuity (r = 0.349; 0.276; 0.307) (p < .001). RNFL thickness around the optic nerve disc measured preoperatively was reduced significantly in all four quadrants in PA patients compared with the control group (p < .001). RNFL thickness was reduced significantly only in the temporal quadrant in PA patients with suprasellar extension compared with the patients without suprasellar extension (p = .009). The temporal RNFL thickness showed the strongest positive correlation with the distance between optic chiasm and PA (r = 0.401, p < .001), while the superior, nasal and, inferior RNFL quadrants showed a weak (r = 0.079; 0.074; 0.113) or not significant (r = 0.351; 0.380; 0.180) correlation with the distance between the optic chiasm and PA. The chiasmal right side, middle part, left side heights correlated significantly with RNFL thickness in all quadrants (p < .05). Our results indicate that suprasellar extension in PA patients causes visual disturbances.

Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL–17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion. IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

Association of FGFR2 rs2981582, SIRT1 rs12778366, STAT3 rs744166 gene polymorphisms with pituitary adenoma

The aim of the present study was to determine the association between sirtuin 1 (SIRT1), fibroblast growth factor receptor 2 (FGFR2) and signal transducer and activator of transcription 3 (STAT3) polymorphisms, and pituitary adenoma (PA) development, invasiveness, hormonal activity and recurrence. The present study included 143 patients with a diagnosis of PA. The reference group involved 808 healthy subjects. The genotyping of SIRT1 rs12778366, FGFR2 rs2981582 and STAT3 rs744166 was performed using the quantitative polymerase chain reaction method. The SIRT1 rs12778366 polymorphism analysis in the overall group revealed differences in the genotype distribution between patients with PA and control group subjects. The rs12778366 T/C genotype was observed to be different in non-invasive, non-recurrent and inactive PA subgroups compared with the control group, while the C/C genotype was observed to be different in invasive, recurrent and active PA subgroups compared with the control group. STAT3 rs744166 polymorphism analysis in the overall group revealed differences in the genotype distribution between patients with PA and the control groups. The rs744166 G/G genotype was observed to be different in invasive, non-recurrent and active PA subgroups compared with the control group, while the rs744166 A/A genotype was observed to be different in the active PA subgroup compared with the control group, and was also different in terms of invasiveness and recurrence in PA subgroups. The present study demonstrated that SIRT1 rs12778366 is associated with pituitary adenoma development while STAT3 rs744166 is associated with PA invasiveness, hormonal activity and recurrence.

Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development?

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.

The Application of a New Maximum Color Contrast Sensitivity Test to the Early Prediction of Chiasma Damage in Cases of Pituitary Adenoma: The Pilot Study

Purpose Our objective was to estimate the maximum color contrast sensitivity (MCCS) thresholds in individuals with chiasma opticum damage. Methods The pilot study tested 41 people with pituitary adenoma (PA) and 100 age- and gender-matched controls. Patients were divided into two groups according to PA size, PA ≤1 cm or PA >1 cm. A new MCCS test program was used for color discrimination. Results The mean total error score (TES) of MCCS was 1.8 in the PA ≤1 cm group (standard deviation [SD], 0.38), 3.5 in the PA >1 cm group (SD, 0.96), and 1.4 in the control group (SD, 0.31; p < 0.001). There was a positive correlation between tumor size and MCCS result (r = 0.648, p < 0.01). In the group that had PA-producing hormones, the TES was 2.5 (SD, 1.09), compared to 4.2 value in the non-functioning PA group of patients that did not have clinically significant hormone excess (SD, 3.16; p < 0.01). In patients with normal visual acuity (VA) or visual field MCCS, the TES was 3.3 (SD, 1.8), while that in patients with VA <0.00 was 4.6 (SD, 2.9). Conclusions Results of the MCCS test TES were 1.9 times better in patients with PA ≤1 cm compared to patients with PA >1 cm (p < 0.01). In PA patients with normal VA, the TES was 2.35 times worse than that of healthy persons (p < 0.01).