scholarly journals Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors

2012 ◽  
Vol 25 (7) ◽  
pp. 1033-1039 ◽  
Author(s):  
Roeland F de Wilde ◽  
Christopher M Heaphy ◽  
Anirban Maitra ◽  
Alan K Meeker ◽  
Barish H Edil ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Small Subset ◽  
Pancreatic Neuroendocrine Tumors ◽  
Alternative Lengthening Of Telomeres ◽  
Men 1 ◽  
Alternative Lengthening

scholarly journals Alternative lengthening of telomeres and ATRX/DAXX loss can be reliably detected in FNAs of pancreatic neuroendocrine tumors

2017 ◽  
Vol 125 (7) ◽  
pp. 544-551 ◽  
Author(s):  
Christopher J. VandenBussche ◽  
Derek B. Allison ◽  
Mindy K. Graham ◽  
Vivek Charu ◽  
Anne Marie Lennon ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening

scholarly journals Alternative Lengthening of Telomeres (ALT) in Pancreatic Neuroendocrine Tumors: Ready for Prime-Time in Clinical Practice?

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Claudio Luchini ◽  
Rita T. Lawlor ◽  
Samantha Bersani ◽  
Caterina Vicentini ◽  
Gaetano Paolino ◽  
...  
Keyword(s):  
Clinical Practice ◽  
High Risk ◽  
Neuroendocrine Tumors ◽  
Tumor Biology ◽  
Specific Marker ◽  
Fish Analysis ◽  
Pancreatic Neuroendocrine Tumors ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening ◽  
Pancreatic Origin

Abstract Purpose of Review Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by some types of malignancies, including pancreatic neuroendocrine tumors, to overcome the issue of telomere shortening, thus supporting tumor growth and cell proliferation. This review is focused on the most important achievements and opportunities deriving from ALT assessment in PanNET onco-pathology, highlighting the most promising fields in which such biomarker could be implemented in clinical practice. Recent Findings In pancreatic neuroendocrine tumors (PanNET), ALT is strongly correlated with the mutational status of two chromatin remodeling genes, DAXX and ATRX. Recent advances in tumor biology permitted to uncover important roles of ALT in the landscape of PanNET, potentially relevant for introducing this biomarker into clinical practice. Indeed, ALT emerged as a reliable indicator of worse prognosis for PanNET, helping in clinical stratification and identification of “high-risk” patients. Furthermore, it is a very specific marker supporting the pancreatic origin of neuroendocrine neoplasms and can be used for improving the diagnostic workflow of patients presenting with neuroendocrine metastasis from unknown primary. The activation of this process can be determined by specific FISH analysis. Summary ALT should be introduced in clinical practice for identifying “high-risk” PanNET patients and improving their clinical management, and as a marker of pancreatic origin among neuroendocrine tumors.

CT Radiogenomic Characterization of the Alternative Lengthening of Telomeres Phenotype in Pancreatic Neuroendocrine Tumors

2018 ◽  
Vol 211 (5) ◽  
pp. 1020-1025 ◽  
Author(s):  
Jonathan M. McGovern ◽  
Aatur D. Singhi ◽  
Amir A. Borhani ◽  
Alessandro Furlan ◽  
Kevin M. McGrath ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Neuroendocrine Tumors ◽  
Alternative Lengthening Of Telomeres ◽  
Alternative Lengthening

scholarly journals Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors

2016 ◽  
Vol 23 (9) ◽  
pp. 759-767 ◽  
Author(s):  
M Cives ◽  
M Ghayouri ◽  
B Morse ◽  
M Brelsford ◽  
M Black ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Proliferative Activity ◽  
Dna Methyltransferase ◽  
Predictive Biomarkers ◽  
Pancreatic Neuroendocrine Tumors ◽  
Mgmt Expression ◽  
Methylguanine Dna Methyltransferase ◽  
Response Predictors ◽  
Alternative Lengthening ◽  
Pathway Activation

The capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O6-methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n=52), grade (n=128) and ALT activation (n=46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time.

scholarly journals Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1

2003 ◽  
pp. 39-43 ◽  
Author(s):  
M Peracchi ◽  
D Conte ◽  
C Gebbia ◽  
C Penati ◽  
S Pizzinelli ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Primary Hyperparathyroidism ◽  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Pancreatic Neuroendocrine Tumors ◽  
Men 1 ◽  
Endocrine Neoplasia

OBJECTIVE: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). DESIGN AND METHODS: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent assay in 61 patients with sporadic GEP NET and in 25 with MEN 1 including 16 with GEP NET. Controls were 50 healthy volunteers, 46 patients with pituitary adenoma and 35 patients with primary hyperparathyroidism. RESULTS: The cutoff value for CgA established in our healthy subjects (as mean+2 s.d.) was 20 U/l. CgA levels were above the normal range in 71/77 patients with sporadic or MEN 1-related GEP NETs (92%), in four out of nine MEN 1 patients without GEP NETs (44%), and only in 22/81 control patients with pituitary or parathyroid disease (27%). Furthermore, CgA levels of over 100 U/l occurred in 36/77 patients with GEP NETs (47%) and only in one patient with a non-functioning pituitary adenoma. In the patients with GEP NETs, both tumor burden and secretory activity affected CgA levels, and successful surgical resection was associated with markedly decreased CgA values. CONCLUSIONS: Plasma CgA was confirmed to be a reliable marker for GEP NETs. Moreover, in MEN 1 patients the finding of very high CgA levels strongly suggests the presence of a GEP NET, as both primary hyperparathyroidism and pituitary adenomas rarely cause marked CgA increases.

Progesterone Receptor and PTEN Expression Predict Survival in Patients With Low- and Intermediate-Grade Pancreatic Neuroendocrine Tumors

2014 ◽  
Vol 138 (8) ◽  
pp. 1027-1036 ◽  
Author(s):  
Jeannelyn S. Estrella ◽  
Russell R. Broaddus ◽  
Amber Mathews ◽  
Denái R. Milton ◽  
James C. Yao ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Neuroendocrine Tumors ◽  
Mammalian Target Of Rapamycin ◽  
Negative Regulator ◽  
Small Subset ◽  
Low Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Intermediate Grade ◽  
Low Profile ◽  
Phosphatase And Tensin Homologue

Context.—The PI3K-AKT-mTOR (phosphatidylinositol 3-kinase–AKT–mammalian target of rapamycin) pathway plays a crucial role in a subset of advanced pancreatic neuroendocrine tumors (PanNETs). In breast and endometrial carcinoma, activation of this pathway inhibits progesterone receptor (PR) expression. Objective.—To determine whether combined low expression of PR and phosphatase and tensin homologue (PTEN), a negative regulator of the PI3K-AKT-mTOR pathway, is a prognostic factor. Design.—A total of 160 resected PanNETs (89 low grade and 71 intermediate grade) were analyzed for PR and PTEN immunohistochemical positivity and staining was correlated with metastasis-free survival (MFS) and overall survival (OS). Progesterone receptor staining was scored as positive by using 1% or greater as cutoff. Weak/faint staining in greater than 90% of tumor cells was considered low PTEN positivity. Results.—Most PanNETs (110 cases, 69%) were both PR and PTEN positive, 45 (28%) were either PR or PTEN positive, and only 5 (3%) had a PR-negative and PTEN-low profile. Combined PR-PTEN positivity was significantly associated with MFS in patients with stage I and II disease (P <.001) and OS in all patients (P < .001) and remained a significant predictor of survival after adjusting for other factors. Patients with PR-negative–PTEN-low PanNETs had the shortest median MFS and OS, compared to those with tumors that were either PR or PTEN positive and with tumors positive for both PR and PTEN (P ≤ .001). Conclusion.—Combined immunohistochemical assessment of PR and PTEN may help identify a small subset of PanNETs with more aggressive behavior and may aid in risk stratification.

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