Pancreatic endocrine tumors

Sylvia, L.

doi:10.1038/modpathol.2010.127

Cited by 75 publications

(79 citation statements)

References 50 publications

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“…Based on these criteria, the ENETS system stages PNETs from I-IV as illustrated in Table 2 [5]. On univariate analysis higher stages of IIIa, IIIb and IV were significant for worse prognosis, and on multivariate analysis stage IV was significant [2].…”

Section: Epidemiologymentioning

confidence: 99%

“…As such, PNETs were originally believed to arise from the islets of Langerhans [5] [24]. The islet cells make up 1% -2% of the total pancreatic mass and include a number of cell types that each secrete a certain hormone, including beta cells (insulin), alpha cells (glucagon), delta cells (somatostatin), and PP cells (pancreatic polypeptide) [25].…”

Section: Etiopathogenesismentioning

confidence: 99%

“…Chromosome 1 and 11q loss with gain of 9q are thought to occur early in development as they have been observed in tumours <2 cm, suggesting genetic instability may be associated with development of malignancy [5] Impaired G1/S checkpoint is reported in PNETs. It is hypothesized that mutations of PTEN in PI3K/mTOR signaling and p53 expression lead to tumor progression [9].…”

Section: Molecular Mechanismsmentioning

confidence: 99%

“…By contrast, 93% of both benign and malignant insulinomas have loss of heterozygosity (LOH) on 22q [29]. PNET metastases often have gain of function in chromosomes 4 and 7, with loss of 21q [5]. Specific factors involved in this metastatic process include VEGF-C, MAGE-1, p27, thrombomodulin, and SRC kinases [32].…”

Section: R Kanthan Et Almentioning

confidence: 99%

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Pancreatic Neuroendocrine Tumors in the 21<sup>st</sup> Century—An Update

Kanthan¹,

Senger²,

Ahmed³

et al. 2017

JCT

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Pancreatic neuroendocrine tumors (PNETs) are rare, reported to account for less than 1% -2% of all pancreatic tumors. This, however, is likely an underestimation, as improved radiologic techniques and heightened awareness have resulted in an increase in the detection of incidentalomas, with estimations of true prevalence as high as 10%. The term "PNET" is an umbrella name that encompasses a heterogeneous group of neoplasms each with distinct clinical presentations, diagnostic radiographic features, management principles, and tumor/patient outcomes. In this context, accurate diagnosis is challenging, and management guidelines remain unclear. A high degree of clinical suspicion is required for best patient management. This manuscript provides an update on PNETs in the 21 st century, in which we re-examine the terminology, epidemiology, classification, etiopathogenesis, radiographic and histopathologic diagnostic features, management for localized and metastatic disease, as well as a review of features defining functional and non-functional PNETS, and finally deliberates on the prognosis and predictive features of this unpredictable and largely unfathomable neoplasm.

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Section: Epidemiologymentioning

confidence: 99%

Section: Etiopathogenesismentioning

confidence: 99%

Section: Molecular Mechanismsmentioning

confidence: 99%

Section: R Kanthan Et Almentioning

confidence: 99%

See 2 more Smart Citations

Pancreatic Neuroendocrine Tumors in the 21<sup>st</sup> Century—An Update

Kanthan¹,

Senger²,

Ahmed³

et al. 2017

JCT

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“…Endocrine tumors that develop from pancreatic islet cells are highly heterogeneous (3). Although poorly differentiated endocrine tumors of the pancreas exist, the cause and contribution of ␤-cell dedifferentiation in the initiation and progression of those lesions remain undetermined.…”

mentioning

confidence: 99%

ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a β-Cell-Induced Dedifferentiation

Ripoche

Charbord

Hennino

et al. 2016

Molecular and Cellular Biology

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cLoss of pancreatic ␤-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote ␤-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor ␤ (TGF-␤)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and ␤-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed ␤-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor ␤-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of ␤-cell maturity, islet plasticity, and progression of insulinoma through its participation in ␤-cell dedifferentiation. Loss of maturity and acquisition of embryonic traits are wellestablished paradigms that contribute to tumor heterogeneity and metastasis (1, 2). Endocrine tumors that develop from pancreatic islet cells are highly heterogeneous (3). Although poorly differentiated endocrine tumors of the pancreas exist, the cause and contribution of ␤-cell dedifferentiation in the initiation and progression of those lesions remain undetermined. Loss of insulin expression has been observed in transgenic mouse models of insulinoma, supporting the existence of a mechanism that reverts the differentiated state of mature ␤ cells in ␤-cell tumors (4, 5). Recently, Landsman et al. demonstrated that elevated Hedgehog/ Gli signaling in ␤ cells alters their identity and leads to the development of undifferentiated endocrine pancreatic tumors (6). Therefore, the participation of ␤-cell dedifferentiation in adult pancreatic pathologies such as islet tumors underscores the need to identify the autocrine factors controlling these mechanisms.While the characterization of signals that regulate ␤-cell development and regeneration is the focus of intense work (7), less is known about mechanisms and molecules that control the differentiation state of mature adult ␤ cells under pathological conditions. The phenomenon of ␤-cell dedifferentiation, characterized by a loss of expression of key ␤-cell genes, such as those encoding insulin, glucose transporter 2 (Glut2), and transcription factors associated with the cells' mature phenotype, was first reported in mouse and recently confirmed in cultured human islets in the absence of any pathological context (8-10). Further evidence has confirmed that the differentiated state of mature adult ␤ cells is not permanent and is lost in response to signals such as oxidative stress and changes in transcriptional profile (11-13). The contribution of ␤-cell dedifferentiation to pathological conditions in vivo is also supported by recent work suggesting that ␤-cell dedifferentiation caused by FoxO1 disruption underlies ␤-cell failure in type...

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