Project description:This dataset contains high throughput sequencing data from Non-functioning pituitary adenomas (NFPAs) together with associated control sections of healthy pituitary which was obtained from formalin-fixed paraffin embeded samples. All of the samles come from patients of Maria Sklodowska-Curie Memorial Cancer Center in Warsaw. All the samples were sequenced using Ion Torrent technology in Maria Sklodwoska-Curie Memorial Cancer Center in Warsaw. They were further processed and used to perform complex analyses using other high-throughput data.
Project description:Giant pituitary adenomas are a subgroup of pituitary adenomas defined by a diameter greater than 4 cm, and they account for 5-14% of adenomas in surgical series. Because of their growth patterns and locations, often involving critical neurovascular structures, they represent a true surgical challenge, and gross total resection is difficult to achieve. There is no consensus on the optimal surgical strategy for giant pituitary adenomas, and, often, integrated multi-staged treatment strategies have been considered. Transcranial or transsphenoidal approaches, alone or combined, according to tumor and patient features are the two main routes. Each of these strategies has pros and cons. The conventional transcranial approach has for a long time been considered the first choice for the removal of giant pituitary adenomas. Currently, with endoscopic techniques, it is also possible to remove lesions that involve the intradural compartment and the adjacent neurovascular structures with the use of extended approaches. Our policy for the management of these lesions is to adopt the endoscopic endonasal approach as the first choice unless the tumor presents significant intracranial extension that results in it being outside the visibility and maneuverability of the endoscopic endonasal route. In these latter cases, we agree that the transcranial approach is more appropriate. However, accurate preoperative evaluation and refined treatment plans for each patient are mandatory to define a proper strategy in order to achieve the most effective long-term result.
Project description:The reasons why some pituitary adenomas are fucntioning(secreting hormones) or not is not well understood. This analysis dig into the transcriptomes of secreting and non-secreting corticotropic adenomas as well as non-fucntioning gonadotropic adenomas.
Project description:PurposeNon-functioning pituitary adenomas (NFPA) have a substantial impact on patients' health status, yet research on the extent of healthcare utilization and costs among these patients is scarce. The objective was to determine healthcare usage, associated costs, and their determinants among patients treated for an NFPA.MethodsIn a cross-sectional study, 167 patients treated for an NFPA completed four validated questionnaires. Annual healthcare utilization and associated costs were assessed through the medical consumption questionnaire (MTA iMCQ). In addition, the Leiden Bother and Needs Questionnaire for pituitary patients (LBNQ-Pituitary), Short Form-36 (SF-36), and EuroQol (EQ-5D) were administered. Furthermore, age, sex, endocrine status, treatment, and duration of follow-up were extracted from the medical records. Associations were analyzed using logistic/linear regression.ResultsAnnual healthcare utilization included: consultation of an endocrinologist (95% of patients), neurosurgeon (14%), and/or ophthalmologist (58%). Fourteen percent of patients had ≥1 hospitalization(s) and 11% ≥1 emergency room visit(s). Mean overall annual healthcare costs were € 3040 (SD 6498), highest expenditures included medication (31%), inpatient care (28%), and specialist care (17%). Factors associated with higher healthcare utilization and costs were greater self-perceived disease bother and need for support, worse mental and physical health status, younger age, and living alone.ConclusionHealthcare usage and costs among patients treated for an NFPA are substantial and were associated with self-perceived health status, disease bother, and healthcare needs rather than endocrine status, treatment, or duration of follow-up. These findings suggest that targeted interventions addressing disease bother and unmet needs in the chronic phase are needed.
Project description:Hypopituitarism tends to occur in large pituitary adenomas. However, similar tumors could present with strikingly different hormonal deficiencies. In this study, we looked at MRI characteristics in non-functioning pituitary adenomas (NFPA), which could predict secondary adrenal insufficiency (SAI) and central hypothyroidism (CHT). We reviewed the files of patients with NFPA attending our clinic. Tumor size, invasiveness, MR-signal intensity, and gadolinium enhancement in preoperative MRI were recorded along with documented presurgical hypopituitarism profile. Logistic regression was used to predict SAI, CHT, or both (SAI/CHT) based on MRI and demographic parameters. Receiver operating characteristic curves were used to determine their diagnostic utility. One hundred twenty-one patients were included in the study. Older age (P = 0.021), male sex (P = 0.043), stalk deviation (P < 0.0001), contrast enhancement (P = 0.029), and optic chiasma compression (P = 0.012) were associated with SAI/CHT. Adenoma vertical height, largest diameter, and estimated volume were also strongly associated with SAI/CHT (P < 0.0001). These associations remained significant in a multivariate analysis. No tumor smaller than 12 mm in vertical height, 17 mm in largest diameter, or 0.9 cm3 in volume was associated with SAI/CHT. At cut-off ≥18 mm for vertical height, ≥23 mm for largest diameter, and ≥3.2 cm3 the sensitivity was around 90-92% for detecting SAI/CHT. Only vertical height was significantly associated with any one or more pituitary hormonal deficit (P = 0.001). In conclusion, adenoma size, independent of the measurement used, remains the best predictor of SAI/CHT in NFPA. Dynamic testing to rule out SAI is probably indicated in adenomas larger than 18 mm vertical height, 23 mm largest diameter and 3.2 cm3 adenoma volume.
Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).
Project description:Non-functioning pituitary adenomas (NFPAs) are benign lesions in the pituitary gland with important morbidities. In this study, based on a bioinformatics analysis to identify the genes and pathways that display significant differences between tumour tissues of NFPA patients and normal pituitary tissues, we selected lncRNAs related to cAMP and oxidative phosphorylation pathways, namely DNAH17-AS1, LINC00706 and SLC25A5-AS1. Then, we aimed to investigate by means of RT-qPCR, the expression of these lncRNAs along with two other lncRNAs, namely CADM3-AS1 and MIR7-3HG in NFPA samples compared to that in healthy tissues adjacent to the tumours. Transcripts of DNAH17-AS1, LINC00706 and MIR7-3HG were lower in NFPA samples compared with controls (Expression ratios (95% CI) = 0.43 (0.23-0.78), 0.58 (0.35-0.96) and 0.58 (0.35-0.96); p-values = 0.009, 0.025 and 0.036, respectively). AUC values of ROC curves of DNAH17-AS1, LINC00706 and MIR7-3HG were 0.62, 0.61 and 0.62, respectively. Expression of CADM3-AS1 was associated with the gender of patients in a way that it was lower in female patients (p-value = 0.04). The level of SLC25A5-AS1 was lower in subjects with disease duration lower than 1 year (p-value = 0.048). We showed dysregulation of three lncRNAs in NFPA tissues and potentiates these lncRNAs as important regulators of pathogenic events in these tumours.
Project description:AimThe WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling.MethodsWithin the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard.ResultsBased on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes.ConclusionsAccording to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.