scholarly journals The Role of T-box Transcription Factor in a Pituitary Adenoma Diagnostic Algorithm

2020 ◽  
Author(s):  
William C. McDonald ◽  
Kelsey N. McDonald ◽  
Jordan A. Helmer ◽  
Bridget Ho ◽  
Amber Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Predictive Value ◽  
Pituitary Adenomas ◽  
Adrenocorticotropic Hormone ◽  
Classification Tree ◽  
Null Cell ◽  
Steroidogenic Factor 1 ◽  
Cluster Analyses ◽  
T Box

Context.— We previously examined pituitary adenomas with immunohistochemical (IHC) stains for steroidogenic factor 1, Pit-1, anterior pituitary hormones, cytokeratin CAM 5.2, and the α-subunit of human chorionic gonadotropin and found that a screening panel comprising stains for steroidogenic factor 1, Pit-1, and adrenocorticotropic hormone successfully classified most cases and reduced the overall number of stains required. Objectives.— To examine the potential role of IHC stain for T-box transcription factor (Tpit) in the classification of our series of pituitary adenomas and to update our screening panel as necessary. Design.— We collected 157 pituitary adenomas from 2 institutions and included these in tissue microarrays. Immunostains for Tpit were scored in a blinded fashion using the Allred system. Adenomas were assigned to a gold standard class based on IHC pattern followed by application of available clinical and serologic information. Test characteristics were calculated. Correlation analyses, cluster analyses, and classification tree analyses were used to see whether IHC staining patterns reliably reflected adenoma class. Results.— Of the cases collected, 147 (93.6%) had sufficient material for Tpit analysis. IHC stain for Tpit identified 8 null cell adenomas (all nonfunctioning clinically) as silent corticotrophs; Tpit stains showed better sensitivity, specificity, positive predictive value, and negative predictive value than IHC for adrenocorticotropic hormone and cytokeratin CAM 5.2. Correlation analyses continued to show the expected relationships among IHC stains. Cluster analyses showed grouping of adenomas into clinically consistent groups. Classification tree analysis underscored the central role of transcription factor IHC stains, including Tpit, in adenoma classification. Conclusions.— Substitution of Tpit stain for the adrenocorticotropic hormone stain improves our prior algorithm by reducing the number of false-negatives and false-positives. As a result, fewer adenomas are classified as null cell adenoma, and more adenomas are classified as silent corticotroph adenoma.

scholarly journals Assessing the role of the T-box transcription factor Eomes in B cell differentiation during either Th1 or Th2 cell-biased responses

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208343 ◽  
Author(s):  
Lucy Cooper ◽  
Lauren Hailes ◽  
Amania Sheikh ◽  
Colby Zaph ◽  
Gabrielle T. Belz ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
B Cell ◽  
B Cell Differentiation ◽  
T Box ◽  
Th2 Cell

scholarly journals Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma

2016 ◽  
Vol 141 (1) ◽  
pp. 104-112 ◽  
Author(s):  
William C. McDonald ◽  
Nilanjana Banerji ◽  
Kelsey N. McDonald ◽  
Bridget Ho ◽  
Virgilia Macias ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Gold Standard ◽  
Anterior Pituitary ◽  
Adrenocorticotropic Hormone ◽  
Pituitary Hormones ◽  
Ease Of Use ◽  
Null Cell ◽  
Steroidogenic Factor 1 ◽  
Α Subunit ◽  
Anterior Pituitary Hormones

Context.—Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. Objective.—To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. Design.—We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. Results.—The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. Conclusions.—Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

scholarly journals Differential Regulation of Proopiomelanocortin and Pituitary-Restricted Transcription Factor (TPIT), a New Marker of Normal and Adenomatous Human Corticotrophs

2003 ◽  
Vol 88 (7) ◽  
pp. 3050-3056 ◽  
Author(s):  
Sophie Vallette-Kasic ◽  
Dominique Figarella-Branger ◽  
Michel Grino ◽  
Anne-Marie Pulichino ◽  
Henry Dufour ◽  
...  
Keyword(s):  
Transcription Factor ◽  
In Situ Hybridization ◽  
Pituitary Adenomas ◽  
Experimental Models ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
T Box ◽  
Normal Human ◽  
Human Anterior Pituitary

Since the identification of the pituitary-restricted transcription factor Tpit, a novel T-box factor that is only present in mouse in the two pituitary proopiomelanocortin (POMC)-expressing lineages, no information was available on its pattern of expression in human pituitary. We investigated by immunohistochemistry and in situ hybridization the expression of TPIT in normal human anterior pituitary tissue and in several types of human pituitary adenomas (n = 52). TPIT expression was restricted to the nucleus of normal or adenomatous human corticotroph cells. No specific TPIT immunostaining was detectable in all prolactin (PRL)-, GH-, or gonadotropin-secreting adenomas. In situ hybridization studies demonstrated that TPIT transcripts were coexpressed with POMC mRNA in both secreting and silent corticotroph adenomas, and in normal corticotrophs, whereas TPIT mRNA was not detectable in other types of pituitary adenomas. Unlike POMC, TPIT was not up-regulated by adrenalectomy in rats and did not seem down-regulated in the normal pituitary adjacent to human corticotroph microadenomas. TPIT is the only currently known transcription factor selectively expressed in human normal and adenomatous corticotrophs. In human and experimental models, TPIT and its target gene POMC were thus differentially regulated by glucocorticoids. Moreover, TPIT represents a new marker of POMC-expressing pituitary cells.

scholarly journals Expression of Steroidogenic Factor 1 and Pituitary Specific Transcription Factor 1 in Rat Pituitary Adenomas

2013 ◽  
Vol 26 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Hironobu YASUNO ◽  
Takeshi WATANABE ◽  
Yumiko MIYAMOTO ◽  
Hitoshi KANDORI ◽  
Hideki YAMASAKI ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Pituitary Adenomas ◽  
Steroidogenic Factor 1 ◽  
Specific Transcription Factor ◽  
Rat Pituitary ◽  
Transcription Factor 1

scholarly journals Examining the role of SUMOylation in C. elegans T-box transcription factor TBX-2 function

2011 ◽  
Vol 356 (1) ◽  
pp. 261
Author(s):  
Paul Huber ◽  
Tanya Crum ◽  
Peter Okkema
Keyword(s):  
Transcription Factor ◽  
T Box ◽  
C Elegans

scholarly journals Down-regulation of miR-10a-5p promotes proliferation and restricts apoptosis via targeting T-box transcription factor 5 in inflamed synoviocytes

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Nazim Hussain ◽  
Wenhua Zhu ◽  
Congshan Jiang ◽  
Jing Xu ◽  
Manman Geng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Control Group ◽  
Down Regulation ◽  
T Box ◽  
Proliferation And Apoptosis ◽  
Polymerase Chain

Synoviocytes from rheumatoid arthritis (RA) patients share certain features with tumor cells, such as over proliferation and invasion. Anomalous microRNA (miRNA) expression may participate in the pathogenesis of RA in different ways. The objective of the present study was to observe the role of miR-10a-5p targeting T-box transcription factor 5 (TBX5) gene on synoviocyte proliferation and apoptosis in RA. Human synovial sarcoma cell line, SW982 cells stimulating with interleukin-1β (IL-1β) were transfected with miR-10a-5p mimic and siRNA of TBX5. The real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis were used to evaluate the expression level of miR-10a-5p and TBX5 in SW982 cells respectively. Further, the proliferation and apoptosis of SW982 cells after treatment were determined by cell counting kit (CCK-8) and flow cytometry analysis respectively. We found that the miR-10a-5p showed down-regulated while TBX5 showed up-regulated expression in synoviocytes after stimulation with IL-1β. The miR-10a-5p mimic treatment showed a decline in cell proliferation while the increased rate of cell apoptosis as compared with control. Moreover, knockdown of TBX5 favored the apoptosis and reduced the cell proliferation as compared with control group. We conclude that down-regulation of miR-10a-5p promotes proliferation and restricts apoptosis via targeting TBX5 in inflamed synoviocytes.

A role for prolyl isomerase PIN1 in the phosphorylation-dependent modulation of PRRXL1 function

2017 ◽  
Vol 474 (5) ◽  
pp. 683-697
Author(s):  
Ricardo Soares-dos-Reis ◽  
Ana Sofia Pessoa ◽  
Ana Filipa Dias ◽  
Miguel Falcão ◽  
Mariana Raimundo Matos ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spinal Cord ◽  
Transcription Factor ◽  
Conformational Changes ◽  
Dorsal Root ◽  
Transcriptional Activity ◽  
Phosphorylation Sites ◽  
Prolyl Isomerase ◽  
Null Cell

Prrxl1 encodes for a paired-like homeodomain transcription factor essential for the correct establishment of the dorsal root ganglion — spinal cord nociceptive circuitry during development. Prrxl1-null mice display gross anatomical disruption of this circuitry, which translates to a markedly diminished sensitivity to noxious stimuli. Here, by the use of an immunoprecipitation and mass spectrometry approach, we identify five highly conserved phosphorylation sites (T110, S119, S231, S233 and S251) in PRRXL1 primary structure. Four are phospho-S/T-P sites, which suggest a role for the prolyl isomerase PIN1 in regulating PRRXL1. Accordingly, PRRXL1 physically interacts with PIN1 and displays diminished transcriptional activity in a Pin1-null cell line. Additionally, these S/T-P sites seem to be important for PRRXL1 conformation, and their point mutation to alanine or aspartate down-regulates PRRXL1 transcriptional activity. Altogether, our findings provide evidence for a putative novel role of PIN1 in the development of the nociceptive system and indicate phosphorylation-mediated conformational changes as a mechanism for regulating the PRRXL1 role in the process.

scholarly journals Somatotroph Adenomas have a Predilection to Invade the Cavernous Sinus and Resection of the Medial Wall of the Cavernous Sinus Offers the Highest Potential for Biochemical Remission in Acromegaly

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A648-A649
Author(s):  
Ahmed Mohyeldin ◽  
Laurence Katznelson ◽  
Juan Fernandez-Miranda
Keyword(s):  
Positive Predictive Value ◽  
Cavernous Sinus ◽  
Predictive Value ◽  
Pituitary Adenomas ◽  
Medial Wall ◽  
Null Cell ◽  
Intraoperative Evaluation ◽  
Remission Rates ◽  
Biochemical Remission ◽  
Wall Invasion

Abstract Recurrence and remission rates vary widely among different histological subtypes of pituitary adenoma. Invasion of the medial wall of the cavernous sinus is a known mechanism that may account for such failed clinical outcomes as its removal has long been considered unattainable. The use of modern endoscopic techniques allows for direct intraoperative evaluation of invasion and resection of the medial wall of the cavernous sinus with low morbidity when performed by highly experienced surgeons. In this retrospective study we evaluated 105 consecutive primary pituitary adenomas operated by a single surgeon including 28 corticotroph, 27 gonadotroph, 24 somatotroph, 15 lactotroph, 5 null-cell, 5 plurihormonal, and 1 dual adenoma; 53 caused hypersecretory syndromes, specifically acromegaly (30), hyperprolactinemia (15) and Cushing’s disease (8). In each case, we performed meticulous intraoperative inspection of the medial wall with its surgical removal when invasion was suspected, regardless of functional status. Medial wall resection was performed in 46% of pituitary adenomas, and 38/48 walls confirmed pathologic evidence of invasion rendering a positive predictive value of intraoperative evaluation of medial wall invasion of 79%. Furthermore, we show for the first time that the rate of medial wall invasion among pathological subtypes is dramatically different. Somatotroph tumors invaded the medial wall much more often than other adenoma subtypes, 83% intraoperatively and 71% histologically, followed by plurihormonal tumors (40%) and gonadotrophs (33%), both with intraoperative positive predictive value of 100%. The least likely to invade were corticotroph, at a rate of 32% intraoperatively and 21% histologically, and null-cell adenomas at 0%. Removal of the medial wall caused no permanent morbidity with no carotid artery injuries and 2 patients with transient diplopia. We report that resecting the medial wall of the cavernous sinus in acromegaly offers the highest potential for biochemical remission with average postoperative day 1 GH levels at 0.96 ug/l and early surgical remission rates at 90% (100% with adjuvant therapy) based on normalization of IGF-1 levels 3 to 6 months after surgery; these results are significantly better than previously reported but longer follow-up is required for definitive conclusions. Our findings may explain the failed biochemical remission rates seen in acromegaly and illustrate the relevance of advanced surgical techniques for successful outcomes in pituitary surgery.

scholarly journals Characterization of Gonadotroph Pituitary Adenomas Based on the Recent 2017 WHO Pituitary Tumor Classification

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A640-A641
Author(s):  
Aviva Cohn ◽  
Chloe Yang Ling Li ◽  
Samantha Elena Hoffman ◽  
Ana Paula Abreu-Metzger ◽  
Joseph Castlen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cavernous Sinus ◽  
Tumor Size ◽  
Pituitary Adenomas ◽  
World Health ◽  
Pituitary Hormone ◽  
Pituitary Insufficiency ◽  
Null Cell ◽  
Cavernous Sinus Invasion

Abstract Introduction: More than 20% of pituitary adenomas are nonfunctional, the majority of which are of gonadotroph origin. Whereas previously, immunohistochemistry of pituitary hormones was used to classify adenoma subtypes, in 2017 the World Health Organization (WHO) reclassified pituitary adenomas using transcription factor expression in addition to immunohistochemistry. With this change, clinically nonfunctional gonadotroph adenomas can be distinguished among: (1) those staining for the transcription factor SF-1 and gonadotropins FSH and/or LH (FSH/LH+), (2) those that stain for SF-1 but not for FSH or LH (FSH/LH- SF1+), and (3) true null cell adenomas. It is unclear whether these three subgroups behave similarly clinically, or if they have distinct manifestations or outcomes. Our aim was to characterize these subgroups in regard to tumor size, recurrence and pituitary insufficiency. Methods: In a retrospective chart review, 71 patients from 2017-2020 who presented to the hospital for transsphenoidal resection of clinically nonfunctioning pituitary adenomas were reviewed. All patients with pituitary adenomas that stained positive for SF-1 and negative for T-PIT and PIT-1, and tumors that were negative for all three transcription factors were evaluated. Those lacking clinical data were excluded. Clinical characteristics examined include: demographics, tumor size, invasion of cavernous sinus, and hormone deficiencies. Results: Of the 71 pituitary tumors, 45% (n=32) stained positive for the beta subunit FSH and/or LH (FSH/LH+) and SF-1, 44% (n=31) stained for SF-1 with negative pituitary hormone stains (FSH/LH- SF1+), and 11% (n=8) were negative for all transcription factors and hormones (true null). All tumors were macroadenomas (>1 cm). While there were >50% males in the FSH/LH+ and FSH/LH- SF1+ groups, in the true null group only 25% of patients were male. Most patients were >50 years old in all 3 groups (81% FSH/LH+, 75% FSH/LH- SF1+, 88% true null). The prevalence of cavernous sinus involvement was 36% in both groups that stained for SF-1, but was 62% in the true null group. Both SF-1+ groups had similar tumor sizes and prevalence of panhypopituitarism (15-21%), but there were more episodes of recurrence since last known follow up in the FSH/LH- SF1+ group (20%), compared to FSH/LH+ tumors (7%). The true null group had ≥50% rates for both panhypopituitarism and recurrence. Conclusions: In this study, we highlighted the category of FSH/LH- SF1+ gonadotroph adenomas and compared these to FSH/LH+ and true null cell tumors. Based on clinical features, FSH/LH- SF1+ gonadotroph adenomas are similar to FSH/LH+ staining pituitary adenomas in regard to age, sex, size, and degree of cavernous sinus invasion, although there were more recurrences in the FSH/LH- SF1+ group. Though less common, our cohort suggests more aggressive tendencies in the true null group compared to SF-1 staining tumors.

The role of transcription factor Egr‐1 in IL‐1 up‐regulation of tubular CD44 expression

Nephrology ◽  
2000 ◽  
Vol 5 (3) ◽  
pp. A92-A92
Author(s):  
Takazoe K ◽  
Foti R ◽  
Hurst La ◽  
Atkins Rc ◽  
Nikolic‐Paterson DJ.
Keyword(s):  
Transcription Factor ◽  
Cd44 Expression
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