scholarly journals EPB41L5 is Associated With the Metastatic Potential of Low-grade Pancreatic Neuroendocrine Tumors

2019 ◽  
Vol 16 (5) ◽  
pp. 309-318 ◽  
Author(s):  
JAMES SALLER ◽  
SHABNAM SEYDAFKAN ◽  
MOHAMMAD SHAHID ◽  
MANOJ GADARA ◽  
MAURO CIVES ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Metastatic Potential ◽  
Low Grade ◽  
Pancreatic Neuroendocrine Tumors

Placenta-Specific 8 Is Overexpressed and Regulates Cell Proliferation in Low-Grade Human Pancreatic Neuroendocrine Tumors

2019 ◽  
Vol 110 (1-2) ◽  
pp. 23-34 ◽  
Author(s):  
Marina Tatura ◽  
Harald Schmidt ◽  
Mikail Haijat ◽  
Maren Stark ◽  
Anja Rinke ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Western Blot ◽  
Neuroendocrine Tumors ◽  
Cell Cycle Progression ◽  
Early Stage ◽  
Metastatic Potential ◽  
Low Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
And Function

Background/Aims: Many aspects of the biology of pancreatic neuroendocrine tumors (PanNETs), including determinants of proliferative, invasive, and metastatic potential, remain poorly understood. Placenta-specific 8 (PLAC8), a gene with unknown molecular function, has been reported to have tumor-promoting roles in different human malignancies, including exocrine pancreatic cancer. Since preliminary data suggested deregulation of PLAC8 expression in PanNET, we have performed detailed analyses of PLAC8 expression and function in human PanNET. Methods: Primary tissue from PanNET patients was immunohistochemically stained for PLAC8, and expression was correlated with clinicopathological data. In vitro, PLAC8 expression was inhibited by siRNA transfection in PanNET cell lines and effects were analyzed by qRT-PCR, Western blot, and proliferation assays. Results: We report that PLAC8 is expressed in the majority of well-differentiated human PanNETs, predominantly in early-stage and low-grade tumors. SiRNA-mediated knockdown of PLAC8 in PanNET cells resulted in decreased proliferation and viability, while apoptosis was not induced. Mechanistically, these effects were mediated by attenuation of cell cycle progression, as Western blot analyses demonstrated upregulation of the tumor suppressor p21/CDKN2A and downregulation of the cell cycle regulator Cyclin D1 as well as reduced levels of phosphorylated ribosomal protein s6 and retinoblastoma protein. Conclusion: Our findings establish PLAC8 as a central mediator of cell growth in a subset of human PanNET, providing evidence for the existence of distinct molecular subtypes within this class of tumors.

Mo1478 KI-67 Cytological Index Can Distinguish Low Grade From High Grade Pancreatic Neuroendocrine Tumors: a Comparative Cyto-Histological Study of 53 Cases

2014 ◽  
Vol 79 (5) ◽  
pp. AB452
Author(s):  
Gabriele Carlinfante ◽  
Paola Baccarini ◽  
Paolo Cecinato ◽  
Debora Berretti ◽  
Tiziana Cassetti ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Histological Study ◽  
Low Grade ◽  
High Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67

Redefining the Ki-67 Index Stratification for Low-Grade Pancreatic Neuroendocrine Tumors: Improving Its Prognostic Value for Recurrence of Disease

2017 ◽  
Vol 25 (1) ◽  
pp. 290-298 ◽  
Author(s):  
Alexandra G. Lopez-Aguiar ◽  
Cecilia G. Ethun ◽  
Lauren M. Postlewait ◽  
Kristen Zhelnin ◽  
Alyssa Krasinskas ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Prognostic Value ◽  
Low Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ki 67

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.

Tumor burden in serotonin secreting pancreatic neuroendocrine tumors after initiating telotristat ethyl.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 367-367
Author(s):  
Susan Giacalone ◽  
Valentina Di Gialleonardo ◽  
Kris Murali ◽  
Vijay N. Joish
Keyword(s):  
Neuroendocrine Tumors ◽  
Clinical Laboratory ◽  
Data Extraction ◽  
Tumor Burden ◽  
Low Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Radiological Data ◽  
Before And After ◽  
Well Differentiated ◽  
Practice Methods

367 Background: Pancreatic neuroendocrine tumors (pNETs) characterized by high serotonin levels and carcinoid syndrome (CS) are rare. We evaluated tumor burden in a subgroup of patients with pNETS from the real-world TELEACE study before and after initiating telotristat ethyl (TE) in US clinical practice. Methods: Detailed methods of the TELEACE study have been reported previously. This was a retrospective, single arm, pre-post physician panel-based chart review of patients who received TE for at least 6 months. Descriptive statistics analyzed demographic, clinical, laboratory and radiological data extracted from medical charts of TELEACE patients with pNETS. Results: Fifty-two patients with pNETS initiating TE were eligible for this analysis. The average age at the time of TE initiation was 60+10.4 years; 64% were males. The majority of patients had well-differentiated (60%) tumors and low-grade (54%) tumor status. Patients received TE for an average of 11.5+7.84 months, and 21% were still receiving TE at the time of data extraction. Diarrhea and flushing were the most common CS symptoms recorded at the time of TE initiation. Urinary 5-HIAA levels were reported for 9 patients before and for 2 patients after TE initiation. Mean (median) 5-HIAA levels before and after TE initiation were 693 (211) and 22 (22) µmol/24h, respectively. Significant mean reduction in tumor size of 0.67 cm after TE initiation (P = 0.017) was observed. Conclusions: This subgroup analysis of the TELEACE study population showed that the addition of TE to somatostatin analog treatment may positively impact tumor burden for patients with functional pNETs.

The management of small asymptomatic pancreatic neuroendocrine tumors: A matched case-control study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 239-239
Author(s):  
Eran Sadot ◽  
Diane Lauren Reidy ◽  
Laura H. Tang ◽  
Mithat Gonen ◽  
Michael Ian D'Angelica ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Size ◽  
Operative Management ◽  
Clinicopathological Characteristics ◽  
Low Grade ◽  
Pancreatic Neuroendocrine Tumors ◽  
Resection Group ◽  
Imaging Characteristics ◽  
Initial Imaging

239 Background: Overdiagnosis and overtreatment has become an evolving challenge for several cancer sub-types. We hypothesized that a substantial portion of incidentally diagnosed small pancreatic neuroendocrine tumors(PanNET) are overtreated as a result of overdiagnosis and that non-operative management may be reasonable for selected patients. Methods: Consecutive patients evaluated for incidentally discovered, sporadic, stage I-II PanNET were analyzed retrospectively. Diagnosis was determined either by pathology or unequivocal imaging characteristics. Patients selected for radiographic surveillance (RS) were matched with patients who underwent resection based on tumor size at initial imaging. Clinicopathological characteristics were compared between the groups. Results: During the study period (2000-2013), RS was recommended for 80 patients, and 79 matched patients underwent resection (resection group). Pathologic diagnosis was obtained in 42 (53%) of the 80 RS patients. Median initial tumor size was similar between the RS vs resection groups (1.2cm (0.8-1.7) vs 1.3 cm (1-1.9), respectively, p=0.4). The resection group was younger and had a longer median follow-up compared to the RS group (58 vs 65 years, p<0.001; 50 vs 29 months, p=0.006; respectively). At the time of last follow-up of the RS group, median tumor size had not changed (1.2cm, p=0.4), no patient had developed metastases, and no patient had experienced radiographic changes in the primary tumor that prompted resection. Within the resection group, low-grade (G1) pathology was recorded in 74 (95%) tumors, one patient had node positive disease, and five developed recurrence (6%). The postoperative complication rate was 36%. No patient in either group died from disease. Death from other causes occurred in 7 out of 159(4%) patients. Conclusions: In this study, no patient who was selected for observation developed metastases or died from disease after a median follow-up of almost 2.5 years.Radiographic surveillance for stable, small, incidentally discovered PanNETs is reasonable in selected patients.

scholarly journals DAXX mutations as potential genomic markers of malignant evolution in small nonfunctioning pancreatic neuroendocrine tumors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mauro Cives ◽  
Stefano Partelli ◽  
Raffaele Palmirotta ◽  
Domenica Lovero ◽  
Barbara Mandriani ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Tumor Size ◽  
Multivariable Analysis ◽  
Metastatic Potential ◽  
Cumulative Number ◽  
Pancreatic Neuroendocrine Tumors ◽  
Driver Genes ◽  
Genomic Markers ◽  
Molecular Machinery ◽  
Well Differentiated

AbstractManagement of localized well-differentiated pancreatic neuroendocrine tumors (panNETs) is controversial and primarily dependent on tumor size. Upfront surgery is usually recommended for tumors larger than 2 cm in diameter since they frequently show metastatic potential, whereas smaller panNETs are generally characterized by an indolent clinical course, with a rate of relapse or metastasis below 15%. To explore whether increased tumor size is paralleled by genomic variations, we compared the rate and the mutational patterns of putative driver genes that are recurrently altered in these tumors by investigating differential cohorts of panNET surgical specimens smaller (n = 27) or larger than 2 cm (n = 29). We found that the cumulative number of mutations detected in panNETs >2 cm was significantly higher (p = 0.03) relative to smaller tumors, while mutations of DAXX were significantly more frequent in the cohort of larger tumors (p = 0.05). Moreover, mutations of DAXX were associated with features of malignancy including increased grade, nodal involvement and lymphovascular invasion, and independently predicted both relapse after surgery (p = 0.05) and reduced DFS in multivariable analysis (p = 0.02). Our data suggest that alterations of the DAXX/ATRX molecular machinery increase the malignant potential of panNETs, and that identification of mutations of DAXX/ATRX in small, nonfunctioning tumors can predict the malignant progression observed in a minority of them.

Clinical Prognosticators of Metastatic Potential in Patients with Small Pancreatic Neuroendocrine Tumors

2021 ◽  
Author(s):  
Eduardo A. Vega ◽  
Onur C. Kutlu ◽  
Sylvia V. Alarcon ◽  
Omid Salehi ◽  
Vera Kazakova ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Metastatic Potential ◽  
Pancreatic Neuroendocrine Tumors
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