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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2017; 9(6): 235-250
Published online Jun 15, 2017. doi: 10.4251/wjgo.v9.i6.235
Detecting circulating tumor material and digital pathology imaging during pancreatic cancer progression
Radim Moravec, Rao Divi, Mukesh Verma
Radim Moravec, Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States
Rao Divi, Mukesh Verma, Methods and Technologies Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, United States
Author contributions: Moravec R wrote the paper; Divi R and Verma M contributed equally by providing guidance and editorial review.
Supported by Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, Rockville, MD 22805, United States.
Conflict-of-interest statement: The authors have no conflicts of interest to report in preparing this work including but not limited to financial, commercial, personal, political, intellectual or religious interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mukesh Verma, PhD, Branch Chief, Methods and Technologies Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Rockville, MD 20850, United States. vermam@mail.nih.gov
Telephone: +1-240-2766889 Fax: +1-240-2767921
Received: January 4, 2017
Peer-review started: January 7, 2017
First decision: February 17, 2017
Revised: March 4, 2017
Accepted: March 23, 2017
Article in press: March 24, 2017
Published online: June 15, 2017
Abstract

Pancreatic cancer (PC) is a leading cause of cancer-related death worldwide. Clinical symptoms typically present late when treatment options are limited and survival expectancy is very short. Metastatic mutations are heterogeneous and can accumulate up to twenty years before PC diagnosis. Given such genetic diversity, detecting and managing the complex states of disease progression may be limited to imaging modalities and markers present in circulation. Recent developments in digital pathology imaging show potential for early PC detection, making a differential diagnosis, and predicting treatment sensitivity leading to long-term survival in advanced stage patients. Despite large research efforts, the only serum marker currently approved for clinical use is CA 19-9. Utility of CA 19-9 has been shown to improve when it is used in combination with PC-specific markers. Efforts are being made to develop early-screening assays that can detect tumor-derived material, present in circulation, before metastasis takes a significant course. Detection of markers that identify circulating tumor cells and tumor-derived extracellular vesicles (EVs) in biofluid samples offers a promising non-invasive method for this purpose. Circulating tumor cells exhibit varying expression of epithelial and mesenchymal markers depending on the state of tumor differentiation. This offers a possibility for monitoring disease progression using minimally invasive procedures. EVs also offer the benefit of detecting molecular cargo of tumor origin and add the potential to detect circulating vesicle markers from tumors that lack invasive properties. This review integrates recent genetic insights of PC progression with developments in digital pathology and early detection of tumor-derived circulating material.

Keywords: Circulating tumor cells, Digital pathology, Early detection, Exosomes, Pancreatic cancer

Core tip: Pancreatic cancer (PC) is a leading cause of cancer-related death. PC mutations accumulate 20 years before patient death with metastatic mutations occurring late in the process. Metastatic risk increases dramatically when tumor diameter is greater than 1 cm. Most PC cases are diagnosed at late metastatic stages when survival is short. Outcomes could be improved if non-invasive methods could detect early stages of the disease and guide treatment decisions. Recent studies indicate this may be possible with application of digital pathology imaging, screening of CA 19-9 with additional markers, and detecting circulating tumor material in early-stage PC patients.