Hypermethylation of thep16/CDKN2A/MTS1 gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas

Author(s):  
David J. Simpson ◽  
John E. Bicknell ◽  
Anne Marie McNicol ◽  
Richard N. Clayton ◽  
William E. Farrell
2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Petr Matoušek ◽  
Petr Buzrla ◽  
Štefan Reguli ◽  
Jan Krajča ◽  
Jana Dvořáčková ◽  
...  

Introduction. Nonfunctional pituitary adenomas are treated surgically, and even partial resection can improve or eliminate clinical symptoms. Notably, progression requires further intervention, which presents an increased risk, especially in older patients. This study investigated whether the histopathological characteristics of nonfunctional adenomas could predict recurrence. Materials and Methods. Data were obtained retrospectively from 30 patients who underwent surgery for the partial resection of pituitary adenomas. Remnant tumor growth was observed in 17 patients, while the residual tumor was unchanged more than 7 years after surgery in 13 patients. Statistical analysis was performed to investigate correlations between remnant tumor progression and tumor histopathological findings, including protein expression of p21, p27, p53, and Ki-67. Results and Discussion. Remnant tumors that demonstrated regrowth showed significantly higher protein expression of p21 and Ki-67. Expression of the p53 tumor suppressor was also higher in this group, but the difference was at the limit of statistical significance. Conclusion. Tumors with high expression of p21 and p53 and with a high Ki-67 index were more likely to show residual pituitary adenoma progression. Such cases should undergo frequent radiological examination and timely reoperation, and radiosurgery should be considered.


Neurosurgery ◽  
2015 ◽  
Vol 79 (3) ◽  
pp. 406-417 ◽  
Author(s):  
Sean M. Barber ◽  
Bin S. Teh ◽  
David S. Baskin

Abstract BACKGROUND Early results of postoperative fractionated stereotactic radiotherapy (FSRT) for functional and nonfunctional pituitary adenomas appear promising, but the majority of available evidence draws from small series with insufficient follow-up data to draw meaningful conclusions. OBJECTIVE To evaluate the long-term outcomes of a large series of patients undergoing FSRT for both functional and nonfunctional pituitary adenomas with the Novalis system (Brain LAB, Heimstetten, Germany). METHODS Chart data for 75 consecutive patients undergoing FSRT for a pituitary tumor (21 functional and 54 nonfunctional adenomas) at our institution between January 2004 and June 2013 were reviewed. RESULTS Radiographic progression-free survival was 100% over a mean of 47.8 months of radiographic follow-up (range, 12.0-131.2 months). Hormonal normalization was seen in 69.2% of patients with functional adenomas after FSRT, whereas 30.8% experienced partial hormonal control. Mild, grade I acute adverse effects were observed during radiotherapy treatment in 36 patients (48%), and objective, persistent worsening of vision occurred in a single patient (1.5%) after FSRT. New hormonal deficits were seen in 28.0% of patients after FSRT. Radiographic responses were inversely related to tumor volume. CONCLUSION FSRT delivers radiographic and functional outcomes similar to those seen with stereotactic radiosurgery and conventional radiotherapy with less resultant toxicity. FSRT is most beneficial for smaller tumors (those <3 cm in diameter).


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
M. Doknić ◽  
S. Pekić ◽  
D. Miljić ◽  
I. Soldatović ◽  
V. Popović ◽  
...  

There are only a few published studies related to the population-based etiology of hypopituitarism. New risks for developing hypopituitarism have been recognized in the last 10 years. Aim. To present data regarding the etiology of hypopituitarism collected in a tertiary center over the last decade. This is a cross-sectional database study. Patients and Methods. We included 512 patients (pts) with hypopituitarism, with a mean age of 45.9 ± 1.7 yrs (range: 18–82; male: 57.9%). Results. Nonfunctional pituitary adenomas were presented in 205 pts (40.5%), congenital causes in 74 pts (14.6%), while acromegaly and prolactinomas were presented in 37 (7.2%) and 36 (7.0%) patients, respectively. Craniopharyngiomas were detected in 30 pts (5.9%), and head trauma due to trauma brain injury-TBI and subarachnoid hemorrhage-SAH in 27 pts (5.4%). Survivors of hemorrhagic fever with renal syndrome (HFRS) and those with previous cranial irradiation were presented in the same frequency (18 pts, 3.5% each). Conclusion. The most common causes of hypopituitarism in our database are pituitary adenomas. Increased awareness of the other causes of pituitary dysfunction, such as congenital, head trauma, extrapituitary cranial irradiation, and infections, is the reason for a higher frequency of these etiologies of hypopituitarism in the presented database.


2000 ◽  
Vol 167 (1) ◽  
pp. 7-13 ◽  
Author(s):  
M Theodoropoulou ◽  
T Arzberger ◽  
Y Gruebler ◽  
Z Korali ◽  
P Mortini ◽  
...  

Thyrotrophin (TSH) synthesis and secretion is under the positive control of thyrotrophin releasing hormone and under the negative control of the thyroid hormones. However, it is hypothesised that TSH has a direct effect on the regulation of its own synthesis through an intrapituitary loop mediated by pituitary TSH receptors (TSH-R). The aim of this investigation was to study the expression of TSH-R in normal human pituitary at mRNA and protein levels, and to compare the pattern of protein expression between different pituitary adenomas. Using RT-PCR we were able to detect TSH-R mRNA in the normal pituitary, and immunohistochemical studies showed TSH-R protein expression in distinct areas of the anterior pituitary. Double immunostaining with antibodies against each of the intrapituitary hormones and S100 revealed that TSH-R protein is present in thyrotrophs and folliculostellate cells. Examination of 58 pituitary adenomas, including two clinically active and two clinically inactive thyrotroph adenomas, revealed TSH-R immunopositivity in only the two clinically inactive thyrotroph adenomas. This study shows, for the first time, the presence of TSH-R protein in the normal anterior pituitary and in a subset of thyrotroph adenomas. The expression of TSH-R in the thyrotroph and folliculostellate cell subpopulations provides preliminary evidence of a role for TSH in autocrine and paracrine regulatory pathways within the anterior pituitary gland.


Author(s):  
Xiaoxu Shen ◽  
Qi Liu ◽  
Jian Xu ◽  
Yang Wang

Abstract Objective This study aimed to investigate the expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), epithelial-cadherin (E- cadherin) and neural-cadherin (N-cadherin) proteins in nonfunctional pituitary adenomas, and their correlation with invasiveness. Method Thirty cases of nonfunctional pituitary adenoma pathological wax specimens were selected from our hospital, including 20 cases of invasive nonfunctional pituitary adenoma (INFPA) and 10 noninvasive nonfunctional pituitary adenomas (NNFPAs). Envision was used to detect IL-6, STAT3, E-cadherin , and N-cadherin in specimens. Statistical methods were used to analyze the correlation between the four proteins and the Knosp classification of nonfunctional pituitary adenomas. Result IL-6 and STAT3 were highly expressed in INFPAs but poorly expressed in NNFPAs. E-cadherin expression in INFPAs was lower than that in NNFPAs. N-cadherin was positive or strongly positive in both groups. Spearman's correlation analysis showed that the expression of IL-6 and STAT3 was positively correlated with Knosp's classification, whereas the expression of E-cadherin was negatively correlated with Knosp classification. Meanwhile, the expression of N-cadherin was not correlated with Knosp's classification. Conclusion The expression of the IL-6, STAT3, E-cadherin proteins were associated nonfunctional pituitary adenomas. However, the expression of N-cadherin was not correlated with nonfunctional pituitary adenomas.


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