TY - JOUR
T1 - Medullary Pancreatic Carcinoma Due to Somatic POLE Mutation
T2 - A Distinctive Pancreatic Carcinoma with Marked Long-Term Survival
AU - Kryklyva, Valentyna
AU - Ter Linden, Esther
AU - Kroeze, Leonie I.
AU - De Voer, Richarda M.
AU - Van Der Kolk, B. Marion
AU - Stommel, Martijn W.J.
AU - Hermans, John J.
AU - Luchini, Claudio
AU - Wood, Laura D.
AU - Hruban, Ralph H.
AU - Nagtegaal, Iris D.
AU - Ligtenberg, Marjolijn J.L.
AU - Brosens, Lodewijk A.A.
N1 - Funding Information:
Abbreviations: CRC - colorectal cancer, EC - endometrial carcinoma, MMR - mismatch repair, MPC - medullary pancreatic carcinoma, MSI - microsatellite instability/instable, MSS - microsatellite stability/stable, PC - pancreatic cancer, From the *Department of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen; †Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht; Departments of ‡Human Genetics, §Surgery, and ||Radiology and Nuclear Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences/ Radboud Institute for Health Sciences, Nijmegen, The Netherlands; ¶Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; and #Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. Received for publication July 18, 2019; accepted May 6, 2020. Address correspondence to: Lodewijk A.A. Brosens, MD, PhD, Department of Pathology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 10 (internal postal code 824), 6525 GA, Nijmegen, The Netherlands (e‐mail: Lodewijk.Brosens@radboudumc.nl). V.K. and E.t.L. contributed equally to this work. This study was supported by a grant from the Dutch Cancer Society (KWF) 2016 10289 and the National Institutes of Health CA 62924. The authors declare no conflict of interest. This report was written with an approval from the patient. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.pancreasjournal.com). Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.
Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Medullary pancreatic carcinoma (MPC) is a rare histological variant of pancreatic ductal adenocarcinoma (PDAC). Because of its rarity, data on the molecular background of MPC are limited. Previous studies have shown that a subset of MPCs is microsatellite instable due to mismatch repair deficiency. Here, we present a unique case of a female patient in her 60s who is a long-term survivor after surgery for pancreatic cancer. The patient had a microsatellite stable MPC with a somatic mutation of the polymerase epsilon gene (POLE). Both microsatellite instable and POLE-mutated cancers are usually associated with high tumor mutational burden and antigen load, resulting in a prominent antitumor immune response and overall better survival. The current case illustrates that, in addition to mismatch repair deficiency, MPC can develop because of a somatic POLE mutation, resulting in a tumor with a high tumor mutational burden and leading to a better prognosis compared with conventional PDAC. This new finding may have important implications in the management of patients with MPC and calls for further studies on the role of POLE in PDAC.
AB - Medullary pancreatic carcinoma (MPC) is a rare histological variant of pancreatic ductal adenocarcinoma (PDAC). Because of its rarity, data on the molecular background of MPC are limited. Previous studies have shown that a subset of MPCs is microsatellite instable due to mismatch repair deficiency. Here, we present a unique case of a female patient in her 60s who is a long-term survivor after surgery for pancreatic cancer. The patient had a microsatellite stable MPC with a somatic mutation of the polymerase epsilon gene (POLE). Both microsatellite instable and POLE-mutated cancers are usually associated with high tumor mutational burden and antigen load, resulting in a prominent antitumor immune response and overall better survival. The current case illustrates that, in addition to mismatch repair deficiency, MPC can develop because of a somatic POLE mutation, resulting in a tumor with a high tumor mutational burden and leading to a better prognosis compared with conventional PDAC. This new finding may have important implications in the management of patients with MPC and calls for further studies on the role of POLE in PDAC.
KW - CRC - colorectal cancer
KW - EC - endometrial carcinoma
KW - MMR - mismatch repair
KW - MPC - medullary pancreatic carcinoma
KW - MSI - microsatellite instability/instable
KW - MSS - microsatellite stability/stable
KW - PC - pancreatic cancer
KW - PDAC - pancreatic ductal adenocarcinoma
KW - POLE - polymerase epsilon
KW - POLE mutation
KW - SPN - solid-pseudopapillary neoplasm
KW - TIL - tumor-infiltrating lymphocyte
KW - TMB - tumor mutational burden
KW - immunotherapy
KW - long-term survival
KW - medullary pancreatic carcinoma
KW - tumor mutational burden
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U2 - 10.1097/MPA.0000000000001588
DO - 10.1097/MPA.0000000000001588
M3 - Article
C2 - 32658072
AN - SCOPUS:85088276871
SN - 0885-3177
VL - 49
SP - 999
EP - 1003
JO - Pancreas
JF - Pancreas
IS - 7
ER -