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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

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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.

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Abbreviations

BD:

Branch duct

CA19-9:

Carbohydrate antigen 19-9

CEA:

Carcinoembryonic antigen

CT:

Computed tomography

EUS:

Endoscopic ultrasound

IPMN:

Intraductal papillary mucinous neoplasm

LOH:

Loss of heterozygosity

MCN:

Mucinous cystic neoplasm

miRNA:

MicroRNA

MPD:

Main pancreatic duct

NGS:

Next-generation sequencing

NPV:

Negative predictive value

PDAC:

Pancreatic ductal adenocarcinoma

PPV:

Positive predictive value

SCA:

Serous cystadenoma

SPN:

Solid pseudopapillary neoplasm

TIL:

Tumor-infiltrating lymphocyte

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Acknowledgements

The authors give thanks to Ms. Helena Vonville for the spreadsheets to guide, organize, and execute the systematic review.

Funding

Dr. Maker is supported by NIH/NCI K08CA190855.

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Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA

    Kiara A. Tulla & Ajay V. Maker

  2. Department of Microbiology and Immunology, University of Illinois at Chicago, 835 S. Wolcott Ave. M/C 790, Chicago, IL, 60612, USA

    Ajay V. Maker

  3. Creticos Cancer Center at AIMMC, Chicago, IL, USA

    Ajay V. Maker

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  1. Kiara A. Tulla
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Tulla, K.A., Maker, A.V. 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. Langenbecks Arch Surg 403, 151–194 (2018). https://doi.org/10.1007/s00423-017-1644-z

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