Outcome after pancreatectomy for neuroendocrine neoplams according to the WHO 2017 grading system: A retrospective multicentric analysis of 138 consecutive patients

Souche, Régis; Coignac, Antoine; Dupuy, Marie; Bertrand, Martin; Raingeart, Isabelle; Guiu, Boris; Herrero, Astrid; Panaro, Fabrizio; Obled, Stéphane; Portalès, Fabienne; Rivière, Benjamin; Ramos, Jeanne; Borie, F.; Quénet, François; Colombo, Pierre‐Emmanuel; Prudhomme, Michel; Assenat, Eric; Fabre, Jean‐Michel

doi:10.1016/j.clinre.2019.08.010

Cited by 5 publications

(2 citation statements)

References 37 publications

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“…Pancreatic NENs are heterogeneous tumors with a highly variable prognosis. Patients with lower grade (G1/G2) tumors were reported to have more favorable survival outcomes than those with higher grade (G3/NEC) tumors 56 , while a small subset of G1/G2 NENs were also aggressive and had a chance of metastasis 57 . Recently, research on pancreatic NENs has attracted much attention but has been restricted by the limited availability of models 20 , 58 .…”

Section: Discussionmentioning

confidence: 99%

Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity

Shi

Yuan

et al. 2022

Nat Commun

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Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.

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Section: Discussionmentioning

confidence: 99%

Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity

Shi

Yuan

et al. 2022

Nat Commun

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“…Due to the rarity and heterogeneity of pancreatic neuroendocrine tumors (PanNETs), it is challenging to identify and classify prognostic factors [1][2][3][4][5]. So far, the prognosis of these tumors largely depends on clinical and histopathological factors, including age, tumor size, mitotic rate, tumor grade, and stage or complete surgical resection [6][7][8]. To evaluate the prognosis, treatment, and classification of PanNETs, the WHO introduced a histological classification system of pancreatic neuroendocrine DOI: 10.1159/000524920 neoplasia (PanNEN) in 2010 [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis

et al. 2022

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Introduction: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published. Methods: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2. Results: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis. Discussion/Conclusion: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.

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Neck transection level and postoperative pancreatic fistula after pancreaticoduodenectomy: A retrospective cohort study of 195 patients

Bardol¹,

Delicque²,

Hermida³

et al. 2020

International Journal of Surgery

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Outcome after pancreatectomy for neuroendocrine neoplams according to the WHO 2017 grading system: A retrospective multicentric analysis of 138 consecutive patients

Cited by 5 publications

References 37 publications

Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity

Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility features associated with drug sensitivity

DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis

Neck transection level and postoperative pancreatic fistula after pancreaticoduodenectomy: A retrospective cohort study of 195 patients

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