Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future

Hao, Scarlett; Takahashi, Caitlin; Snyder, Rebecca A.; Parikh, Alexander A.

doi:10.3390/ijms21031147

Cited by 15 publications

(12 citation statements)

References 68 publications

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“…Additional mutations in TP53 , PIK3CA , and PTEN testing showed 79% sensitivity, 96% specificity for all mucinous pancreatic cysts with advanced neoplasia, showing potential for the role of molecular analyses in risk stratification of cysts. Other genes that have proven useful in risk stratification of IPMNs include SMAD4 , RNF43 , and CDKN2A [ 18 , 21 ].…”

Section: Endoscopic Ultrasound-guided Methodology For Risk Stratificamentioning

confidence: 99%

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

Eiterman¹,

Lahooti²,

Krishna³

2020

WJG

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Pancreatic cancer has a high mortality rate with minimal proven interventions. Intraductal Papillary Mucinous Neoplasms (IPMNs) are known precursor lesions for pancreatic cancer. Identification of pancreatic cysts has improved from advances in abdominal imaging. Despite multiple revisions of the international consensus recommendations and various guidelines by other major societies, successful risk stratification of the malignant potential of mucinous pancreatic cysts remains challenging. Specifically, detection and accurate classification of advanced neoplasia (high-grade dysplasia and/or adenocarcinoma) in IPMNs is suboptimal with current diagnostic strategies. Development of interventional techniques utilizing endoscopic ultrasound include - through-the-needle microforceps biopsy, next-generation or whole genome molecular analysis of cyst fluid, and needle-based confocal laser endomicroscopy. These techniques suffer from a series of limitations in technical success, diagnostic yield, and clinical feasibility, but a combination approach may offer a solution that optimizes their cyst evaluation and risk stratification. Assessment and comparison of these techniques is restricted by lack of adequate surgical specimens for testing of diagnostic accuracy, resulting in a possible sample bias. Additional large-scale multicenter studies are needed to accumulate evidence for the utility and feasibility of their translation into clinical practice. Great strides have been made in pancreatic cyst evaluation, but further research is required to improve diagnostic accuracy and clinical management of IPMNs.

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Section: Endoscopic Ultrasound-guided Methodology For Risk Stratificamentioning

confidence: 99%

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

Eiterman¹,

Lahooti²,

Krishna³

2020

WJG

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“…Next, we compared these proteins with our DEGs to find out how many of our upregulated and downregulated DEGs belong to the class of secretory proteins (which resulted in 31 upregulated and 14 downregulated DEGs). Meanwhile, we have rigorously explored the published literature on mass spectrometryanalysed proteome results and listed all the secretory proteins differentially detected in cyst fluid of malignant IPMNs in those high-throughput studies (Supplementary Table 9) [6,[35][36][37][38]. All of them were high-throughput studies having lots of variations between them.…”

Section: Identification Of the Cyst Fluidmentioning

confidence: 99%

“…Investigation of somatic mutations and chromosomal abnormalities using tumour DNA collected from cyst fluid showed loss of heterozygosity at 9p12 (p16) and 17 p13 (p53) in malignant IPMNs [5]. Cyst fluid gene expression analysis, miRNA profiling, and proteome profiling have also been studied to have an idea of small RNA and protein-based biomarkers for detection of highrisk IPMN [6]. However, there has not been an integration of these multiple studies, and due to this unavailability of cytology and biochemical markers in classifying the pathology of IPMN accurately, the quest for molecular markers capable of detecting IPMNs with high risk of malignancy is still ongoing.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic Analysis and Integration of Transcriptome and Proteome Results Identify Key Coding and Noncoding Genes Predicting Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Saha

Chhatriya

Pramanick

et al. 2021

BioMed Research International

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Background. Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). IPMNs are generally associated with high risk of developing malignancy and therefore need to be diagnosed and assessed accurately, once detected. Existing diagnostic methods are inadequate, and identification of efficient biomarker capable of detecting high-risk IPMNs is necessitated. Moreover, the mechanism of development of malignancy in IPMNs is also elusive. Methods. Gene expression meta-analysis conducted using 12 low-risk IPMN and 23 high-risk IPMN tissue samples. We have also listed all the altered miRNAs and long noncoding RNAs (lncRNAs), identified their target genes, and performed pathway analysis. We further enlisted cyst fluid proteins detected to be altered in high-risk or malignant IPMNs and compared them with fraction of differentially expressed genes secreted into cyst fluid. Results. Our meta-analysis identified 270 upregulated and 161 downregulated genes characteristically altered in high-risk IPMNs. We further identified 61 miRNAs and 14 lncRNAs and their target genes and key pathways contributing towards understanding of the gene regulation during the progression of the disease. Most importantly, we have detected 12 genes altered significantly both in cystic lesions and cyst fluid. Conclusion. Our study reports, for the first time, a meta-analysis identifying key changes in gene expression between low-risk and high-risk IPMNs and also explains the regulatory aspect through construction of a miRNA-lncRNA-mRNA interaction network. The 12-gene-signature could function as potential biomarker in cyst fluid for detection of IPMN with a high risk of developing malignancy.

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“…FPC is defined as at least two first-degree relatives with PDAC, which are not at increased risk from other syndromes [117] . There is a body of literature establishing a link between numerous specific germline mutations and pancreatic cancer: ATM, BRCA1/2, CDKN2A, MLH1, MSH2, PALB2, PMS2, PRSS1, and STK11 [118][119][120][121][122][123][124][125] .…”

Section: Heritable Causes Of Pancreatic Cancer and Ipmnmentioning

confidence: 99%

“…The literature base regarding heritable IPMN is more limited; however, in a 2019 study of resected IPMN tissue Skaro et al [125] found that 7.3% of patients carried germline mutations in one of the 94 genes captured in the TruSight Cancer probe, and 2.9% of patients carried a germline mutation specifically associated with pancreatic cancer. They also found that patients with IPMN and a concurrent invasive cancer were more likely to have pancreatic-specific germline mutations, than patients with IPMN alone [125] . This study suggests that there may be a link between FPC and IPMN development; however, currently there is a paucity of data on the topic.…”

Section: Heritable Causes Of Pancreatic Cancer and Ipmnmentioning

confidence: 99%

Clinical implications of the molecular characterization of intraductal papillary mucinous neoplasms of the pancreas

Peters¹,

Kunstman²

2021

JCMT

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Intraductal papillary mucinous neoplasm (IPMN) is a pre-malignant, mucin-producing epithelial lesion arising from pancreatic ducts. Observational reports define IPMN behavior as ranging from indolent, asymptomatic lesions to dysplasia that sometimes degenerate into pancreatic adenocarcinoma. The goal of IPMN management is riskreducing surgery for high-risk cysts and observation of the remainder. Discriminating high-from low-risk IPMN disease still relies on imaging and clinical cyst characteristics. Here, we review the accepted classification of IPMN including the most common histological subtypes, their clinical features, and currently-accepted high-risk phenotypes. We then deeply examine the known molecular landscape of IPMN, which has largely been derived from post-resection analysis. This includes those gene variants unique to IPMN, chiefly GNAS and RNF43, but also examines the overlap between IPMN and conventional pancreatic adenocarcinoma. Utilizing molecular markers in the clinical setting relies on endoscopically-obtained cyst fluid and presumes that it accurately represents the molecular characteristics of the cystic epithelium. We synthesize existing data on mutational analysis from IPMN cyst fluid and consider the benefits and proper role of current commercially-available cyst fluid molecular analysis kits. We conclude that carefully interpreted molecular analysis of resected IPMN tissue reveals insights into its biology and natural history while cyst fluid analysis offers prognostication and data to guide treatment decisions. However, knowledge gaps remain, especially in characterizing IPMN molecular heterogeneity, time to progression, and correlating cyst fluid genotype data with surveillance strategies. As such, substantial additional research is required before the promise of true molecular guidance of IPMN management can be realized.

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Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future

Cited by 15 publications

References 68 publications

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

Endosonographic diagnosis of advanced neoplasia in intraductal papillary mucinous neoplasms

Bioinformatic Analysis and Integration of Transcriptome and Proteome Results Identify Key Coding and Noncoding Genes Predicting Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Clinical implications of the molecular characterization of intraductal papillary mucinous neoplasms of the pancreas

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