Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Lupinacci, Renato M.; Goloudina, Anastasia R.; Buhard, Olivier; Bachet, Jean‐Baptiste; Maréchal, Raphaël; Demetter, Pieter; Cros, Jérôme; Bardier–Dupas, Armelle; Collura, Ada; Cervera, Pascale; Scriva, Aurélie; Dumont, Sylvie; Hammel, Pascal; Sauvanet, Alain; Louvet, Christophe; Delpéro, Jean‐Robert; Paye, François; Vaillant, Jean‐Christophe; André, Thierry; Closset, Jean; Émile, Jean-François; Laethem, Jean‐Luc Van; Jonchère, Vincent; Alsamad, Issam Abd; Antoine, Martine; Rodenas, Anita; Fléjou, Jean‐François; Dusetti, Nelson; Iovanna, Juan; Duval, Alex; Svrcek, Magali

doi:10.1053/j.gastro.2017.11.009

Cited by 82 publications

(55 citation statements)

References 9 publications

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“…Microsatellite Instability (MSI) is another molecular feature that can be found in PDAC with an incidence between 1 and 2% [30,31] and it is typically associated with a germline mutation in MMR (mismatch repair) genes and IHC (immunohistochemistry) loss of MMR expression [32]. The prevalence of dMMR/MSI in PDAC is likely very low, but data in this regard are inconsistent.…”

Section: Microsatellite Instabilitymentioning

confidence: 99%

Prognostic and predictive factors in pancreatic cancer

et al. 2020

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Pancreatic cancer is one of the leading causes of cancer death worldwide. Its high mortality rate has remained unchanged for years. Radiotherapy and surgery are considered standard treatments in early and locally advanced stages. Chemotherapy is the only option for metastatic patients. Two treatment regimens, i. e. the association of 5-fluorouracil-irinotecan-oxaliplatin (FOLFIRINOX) and the association of nabpaclitaxel with gemcitabine, have been shown to improve outcomes for metastatic pancreatic adenocarcinoma patients. However, there are not standardized predictive biomarkers able to identify patients who benefit most from treatments. CA19-9 is the most studied prognostic biomarker, its predictive role remains unclear. Other clinical, histological and molecular biomarkers are emerging in prognostic and predictive settings. The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

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Section: Microsatellite Instabilitymentioning

confidence: 99%

Prognostic and predictive factors in pancreatic cancer

et al. 2020

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“…Hu et al reported that the dMMR phenotype was present in only 0.8% (7/833) of patients with PDAC [60]. Lupinacci et al also reported a retrospective and multicenter study of MSI status in 443 cases with PDAC including 58 intraductal papillary mucinous neoplasm (IPMN)-associated PDACs [61]. In their report, the MSI-H/dMMR phenotype was present in 5 of 385 (1.3%) non-IPMN-associated PDACs and 4 of 58 (6.9%) IPMN-associated PDACs.…”

Section: Msi Status and Treatment With Icis For Pancreatic Cancermentioning

confidence: 99%

Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers

et al. 2019

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Recent innovations in the next-generation sequencing technologies have unveiled that the accumulation of genetic alterations results in the transformation of normal cells into cancer cells. Accurate and timely repair of DNA is, therefore, essential for maintaining genetic stability. Among various DNA repair pathways, the mismatch repair (MMR) pathway plays a pivotal role. MMR deficiency leads to a molecular feature of microsatellite instability (MSI) and predisposes to cancer. Recent studies revealed that MSI-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, regardless of their primary site, have a promising response to immune checkpoint inhibitors (ICIs), leading to the approval of the anti-programmed cell death protein 1 monoclonal antibody pembrolizumab for the treatment of advanced or recurrent MSI-H/dMMR solid tumors that continue to progress after conventional chemotherapies. This new indication marks a paradigm shift in the therapeutic strategy of cancers; however, when considering the optimum indication for ICIs and their safe and effective usage, it is important for clinicians to understand the genetic and immunologic features of each tumor. In this review, we describe the molecular basis of the MMR pathway, diagnostics of MSI status, and the clinical importance of MSI status and the tumor mutation burden in developing therapeutic strategies against gastrointestinal and hepatobiliary malignancies.

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“…Since it is estimated that only 1%–2% of all pancreatic carcinoma are MMR deficient,148 the number of eligible patients with pancreatic cancer will be small. In contrast, MMR deficiency was reported to be more frequent in acinar cell carcinoma,149 and in intraductal papillary mucinous neoplasms (IPMN)-related tumours as compared with non-IPMN-related tumours 150…”

Section: Introductionmentioning

confidence: 97%

Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

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Öhlund

et al. 2018

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Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.

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Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Cited by 82 publications

References 9 publications

Prognostic and predictive factors in pancreatic cancer

Prognostic and predictive factors in pancreatic cancer

Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers

Stromal biology and therapy in pancreatic cancer: ready for clinical translation?

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