Can We Better Predict the Biologic Behavior of Incidental IPMN? A Comprehensive Analysis of Molecular Diagnostics and Biomarkers in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Overview

Journal Langenbecks Arch Surg

Specialty General Surgery

Date 2017 Dec 9

PMID 29218397

Citations 7

Authors

Kiara A Tulla

Ajay V Maker

Affiliations

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Abstract

Purpose: Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia.

Methods: A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines.

Results: Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia.

Conclusions: Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

Citing Articles

Correlation of GNAS Mutational Status with Oncologic Outcomes in Patients with Resected Intraductal Papillary Mucinous Neoplasms.

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PMID: 40002298 PMC: 11852742. DOI: 10.3390/cancers17040705.

Real-Life Management of Pancreatic Cysts: Simplified Review of Current Guidelines.

Vladut C, Bilous D, Ciocirlan M J Clin Med. 2023; 12(12).

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The tumour immune microenvironment and microbiome of pancreatic intraductal papillary mucinous neoplasms.

Pollini T, Adsay V, Capurso G, Dal Molin M, Esposito I, Hruban R Lancet Gastroenterol Hepatol. 2022; 7(12):1141-1150.

PMID: 36057265 PMC: 9844533. DOI: 10.1016/S2468-1253(22)00235-7.

Multi-Omic Biomarkers as Potential Tools for the Characterisation of Pancreatic Cystic Lesions and Cancer: Innovative Patient Data Integration.

Kane L, Mellotte G, Conlon K, Ryan B, Maher S Cancers (Basel). 2021; 13(4).

PMID: 33673153 PMC: 7918773. DOI: 10.3390/cancers13040769.

GNAS mutation detection in circulating cell-free DNA is a specific predictor for intraductal papillary mucinous neoplasms of the pancreas, especially for intestinal subtype.

Hata T, Mizuma M, Motoi F, Omori Y, Ishida M, Nakagawa K Sci Rep. 2020; 10(1):17761.

PMID: 33082481 PMC: 7576136. DOI: 10.1038/s41598-020-74868-2.

References

Permuth-Wey J, Chen D, Fulp W, Yoder S, Zhang Y, Georgeades C . Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas. Cancer Prev Res (Phila). 2015; 8(9):826-34. PMC: 4560649. DOI: 10.1158/1940-6207.CAPR-15-0094. View

Maker A, Katabi N, Gonen M, DeMatteo R, DAngelica M, Fong Y . Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas. Ann Surg Oncol. 2010; 18(1):199-206. PMC: 4241376. DOI: 10.1245/s10434-010-1225-7. View

Safi F, Schlosser W, Falkenreck S, Beger H . Prognostic value of CA 19-9 serum course in pancreatic cancer. Hepatogastroenterology. 1998; 45(19):253-9. View

Yonezawa S, Goto M, Yamada N, Higashi M, Nomoto M . Expression profiles of MUC1, MUC2, and MUC4 mucins in human neoplasms and their relationship with biological behavior. Proteomics. 2008; 8(16):3329-41. DOI: 10.1002/pmic.200800040. View

Springer S, Wang Y, Dal Molin M, Masica D, Jiao Y, Kinde I . A combination of molecular markers and clinical features improve the classification of pancreatic cysts. Gastroenterology. 2015; 149(6):1501-10. PMC: 4782782. DOI: 10.1053/j.gastro.2015.07.041. View

Berger A, Schwerdel D, Costa I, Hackert T, Strobel O, Lam S . Detection of Hot-Spot Mutations in Circulating Cell-Free DNA From Patients With Intraductal Papillary Mucinous Neoplasms of the Pancreas. Gastroenterology. 2016; 151(2):267-70. DOI: 10.1053/j.gastro.2016.04.034. View

Anand N, Sampath K, Wu B . Cyst features and risk of malignancy in intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis. Clin Gastroenterol Hepatol. 2013; 11(8):913-21. DOI: 10.1016/j.cgh.2013.02.010. View

Maker A, Lee L, Raut C, Clancy T, Swanson R . Cytology from pancreatic cysts has marginal utility in surgical decision-making. Ann Surg Oncol. 2008; 15(11):3187-92. DOI: 10.1245/s10434-008-0110-0. View

Singhi A, Nikiforova M, Fasanella K, McGrath K, Pai R, Ohori N . Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. Clin Cancer Res. 2014; 20(16):4381-9. DOI: 10.1158/1078-0432.CCR-14-0513. View

10.

Wu J, Matthaei H, Maitra A, Dal Molin M, Wood L, Eshleman J . Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011; 3(92):92ra66. PMC: 3160649. DOI: 10.1126/scitranslmed.3002543. View

11.

Permuth-Wey J, Chen Y, Fisher K, McCarthy S, Qu X, Lloyd M . A genome-wide investigation of microRNA expression identifies biologically-meaningful microRNAs that distinguish between high-risk and low-risk intraductal papillary mucinous neoplasms of the pancreas. PLoS One. 2015; 10(1):e0116869. PMC: 4301643. DOI: 10.1371/journal.pone.0116869. View

12.

Sessa F, Solcia E, Capella C, Bonato M, Scarpa A, Zamboni G . Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch. 1994; 425(4):357-67. DOI: 10.1007/BF00189573. View

13.

Jang J, Park Y, Song Y, Lee S, Hwang D, Lim C . Increased K-ras mutation and expression of S100A4 and MUC2 protein in the malignant intraductal papillary mucinous tumor of the pancreas. J Hepatobiliary Pancreat Surg. 2009; 16(5):668-74. DOI: 10.1007/s00534-009-0105-7. View

14.

Bloomston M, Frankel W, Petrocca F, Volinia S, Alder H, Hagan J . MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007; 297(17):1901-8. DOI: 10.1001/jama.297.17.1901. View

15.

Kuboki Y, Shimizu K, Hatori T, Yamamoto M, Shibata N, Shiratori K . Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas. Pancreas. 2014; 44(2):227-35. DOI: 10.1097/MPA.0000000000000253. View

16.

Maker A, Katabi N, Qin L, Klimstra D, Schattner M, Brennan M . Cyst fluid interleukin-1beta (IL1beta) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res. 2011; 17(6):1502-8. PMC: 3065716. DOI: 10.1158/1078-0432.CCR-10-1561. View

17.

Satoh K, Kanno A, Hamada S, Hirota M, Umino J, Masamune A . Expression of Sonic hedgehog signaling pathway correlates with the tumorigenesis of intraductal papillary mucinous neoplasm of the pancreas. Oncol Rep. 2008; 19(5):1185-90. View

18.

Wang H, Chen T, Wang H, Song Y, Li X, Wang J . A systematic review of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity and its Portsmouth modification as predictors of post-operative morbidity and mortality in patients undergoing pancreatic surgery. Am J Surg. 2013; 205(4):466-72. DOI: 10.1016/j.amjsurg.2012.06.011. View

19.

Hiraoka N, Onozato K, Kosuge T, Hirohashi S . Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006; 12(18):5423-34. DOI: 10.1158/1078-0432.CCR-06-0369. View

20.

Kikuchi J, Takashina T, Kinoshita I, Kikuchi E, Shimizu Y, Sakakibara-Konishi J . Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone methyltransferase EZH2, inhibits growth of non-small cell lung cancer cells. Lung Cancer. 2012; 78(2):138-43. PMC: 3472089. DOI: 10.1016/j.lungcan.2012.08.003. View