Microsatellite Instability Analysis and Its Prognostic Value in Invasive Nonampullary Duodenal Adenocarcinoma

Yang G.a· Tanaka T.a· Kinugasa H.b· Kanzaki H.b· Chen M.-X.a· Ichimura K.c· Nakagawa M.d· Jin Z.-S.e· Zheng R.f· Yoshino T.a

Author affiliations

aDepartment of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
bDepartment of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
cDepartment of Pathology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
dDepartment of Endoscopy, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
eDepartment of Pathology, Mudanjiang Medical University, Mudanjiang, China
fMedical Imaging Center, The Mine Hospital of Xu Zhou, Xuzhou, China

Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud Rent for 48h to view Buy Cloud Access for unlimited viewing via different devices Synchronizing in the ReadCube Cloud Printing and saving restrictions apply Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Abstract of Clinical Study

Received: August 27, 2021
Accepted: September 19, 2021
Published online: March 29, 2022

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 5

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Abstract

Purpose: Nonampullary duodenal adenocarcinoma (NADA) is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive NADA, focusing on the microsatellite instability (MSI) phenotype, programmed cell death-ligand 1 (PD-L1) expression, and prognostic factors. Methods: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25, and BAT-26) were amplified for MSI assessment by PCR. Results: The incidence of MSI in invasive NADA was 35.2%. No significant correlation between the MSI phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (p = 0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (p = 0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival (OS) in patients with MSI (p = 0.013) and at early-stage disease (p = 0.000) than in those with microsatellite-stable or at late tumor stages. Univariate and multivariate analyses showed that MSI (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106–0.751, p = 0.011) and early tumor stage (stage I-II) (HR: 8.81, 95% CI: 2.545–30.500, p = 0.001) were independent better prognostic factors of OS. Conclusions: MSI and early tumor stage (stage I-II) were independent better prognostic factors of OS. A high proportion of MSI phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.

© 2022 S. Karger AG, Basel

References Zheng Z, Zhou X, Zhang J, Zhao B, Chen C, Liu X, et al. Nomograms predict survival of patients with small bowel adenocarcinoma: a SEER-based study. Int J Clin Oncol. 2021 Feb;26(2):387–98. Yoshida M, Shimoda T, Abe M, Kakushima N, Kawata N, Takizawa K, et al. Clinicopathological characteristics of non-ampullary duodenal tumors and their phenotypic classification. Pathol Int. 2019 Jul;69(7):398–406. Xue Y, Vanoli A, Balci S, Reid MM, Saka B, Bagci P, et al. Non-ampullary-duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas. Mod Pathol. 2017 Feb;30(2):255–66. Takinami M, Kakushima N, Yoshida M, Sasaki K, Takizawa K, Yabuuchi Y, et al. Endoscopic features of submucosal invasive non-ampullary duodenal carcinomas. J Gastroenterol Hepatol. 2020 May;35(5):821–6. Matsueda K, Kanzaki H, Matsueda K, Nasu J, Yoshioka M, Nakagawa M, et al. The clinicopathological differences of sporadic non-ampullary duodenal epithelial neoplasm depending on tumor location. J Gastroenterol Hepatol. 2019 Sep;34(9):1540–44. Ota R, Sawada T, Tsuyama S, Sasaki Y, Suzuki H, Kaizaki Y, et al. Integrated genetic and epigenetic analysis of cancer-related genes in non-ampullary duodenal adenomas and intramucosal adenocarcinomas. J Pathol. 2020 Nov;252(3):330–42. Ryder NM, Ko CY, Hines OJ, Gloor B, Reber HA. Primary duodenal adenocarcinoma: a 40-year experience. Arch Surg. 2000 Sep;135(9):1070–4; discussion 1074–5. Zenali M, Overman MJ, Rashid A, Broaddus RB, Wang H, Katz MH, et al. Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma. Hum Pathol. 2013 Dec;44(12):2792–8. Kato Y, Takahashi S, Kinoshita T, Shibasaki H, Gotohda N, Konishi M. Surgical procedure depending on the depth of tumor invasion in duodenal cancer. Jpn J Clin Oncol. 2014 Mar;44(3):224–31. Hirashita T, Ohta M, Tada K, Saga K, Takayama H, Endo Y, et al. Prognostic factors of non-ampullary duodenal adenocarcinoma. Jpn J Clin Oncol. 2018 Aug 1;48(8):743–7. Srivastava S, Avvaru AK, Sowpati DT, Mishra RK. Patterns of microsatellite distribution across eukaryotic genomes. BMC Genomics. 2019 Feb 22;20(1):153. Cullis CA. The use of DNA polymorphisms in genetic mapping. Genet Eng. 2002;24:179–89. Yang G, Zheng RY, Jin ZS. Correlations between microsatellite instability and the biological behaviour of tumours. J Cancer Res Clin Oncol. 2019 Dec;145(12):2891–9. Lin A, Zhang J, Luo P. Crosstalk between the MSI status and tumor microenvironment in colorectal cancer. Front Immunol. 2020;11:2039. Liu X, Choi MG, Kim K, Kim KM, Kim ST, Park SH, et al. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathol Res Pract. 2020 Apr;216(4):152881. Overman MJ, Pozadzides J, Kopetz S, Wen S, Abbruzzese JL, Wolff RA, et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. Br J Cancer. 2010 Jan 5;102(1):144–50. Aparicio T, Svrcek M, Zaanan A, Beohou E, Laforest A, Afchain P, et al. Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study. Br J Cancer. 2013 Dec 10;109(12):3057–66. Watari J, Mitani S, Ito C, Tozawa K, Tomita T, Oshima T, et al. Molecular alterations and PD-L1 expression in non-ampullary duodenal adenocarcinoma: associations among clinicopathological, immunophenotypic and molecular features. Sci Rep. 2019 Jul 19;9(1):10526. Brierley JD, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 8th ed. John Wiley & Sons, Ltd; 2017. Sakae H, Kanzaki H, Nasu J, Akimoto Y, Matsueda K, Yoshioka M, et al. The characteristics and outcomes of small bowel adenocarcinoma: a multicentre retrospective observational study. Br J Cancer. 2017 Nov 21;117(11):1607–13. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, et al. Small bowel adenocarcinoma, version 1.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019 Sep 1;17(9):1109–33. Pollack R, Kagan M, Dresner-Pollak R, Neuman T. PD-L1 expression in normal endocrine tissues is not increased despite high incidence of pd-1 inhibitor-associated endocrinopathies. Endocr Pract. 2021 Jan;27(1):34–7. Oda S, Oki E, Maehara Y, Sugimachi K. Precise assessment of microsatellite instability using high resolution fluorescent microsatellite analysis. Nucleic Acids Res. 1997 Sep 1;25(17):3415–20. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A national cancer institute workshop on nicrosatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998 Nov 15;58(22):5248–57. Warth A, Kloor M, Schirmacher P, Bläker H. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP. Mod Pathol. 2011 Apr;24(4):564–70. Choi E, Chang MS, Byeon SJ, Jin H, Jung KC, Kim H, et al. Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas. Diagn Pathol. 2020 Jun 4;15(1):69. Giuffrida P, Arpa G, Grillo F, Klersy C, Sampietro G, Ardizzone S, et al. PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability. Mod Pathol. 2020 Jul;33(7):1398–409. Salem ME, Puccini A, Grothey A, Raghavan D, Goldberg RM, Xiu J, et al. Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers. Mol Cancer Res. 2018 May;16(5):805–12. Klose J, Lasitschka F, Horsch C, Strowitzki MJ, Bruckner T, Volz C, et al. Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma. Scand J Gastroenterol. 2020 Mar;55(3):321–9. Polom K, Marano L, Marrelli D, De Luca R, Roviello G, Savelli V, et al. Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer. Br J Surg. 2018 Feb;105(3):159–67. Yang G, Zheng RY, Tan Q, Dong CJ, Jin ZS. Clinical characteristics and responses to chemotherapy and immune checkpoint inhibitor treatment for microsatellite instability gastric cancer. Am J Cancer Res. 2020;10(12):4123–33. Badalamenti G, Fanale D, Incorvaia L, Barraco N, Listì A, Maragliano R, et al. Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone? Cell Immunol. 2019 Sep;343:103753. Roudko V, Bozkus CC, Orfanelli T, McClain CB, Carr C, O’Donnell T, et al. Shared immunogenic poly-epitope frameshift mutations in microsatellite unstable tumors. Cell. 2020 Dec 10;183(6):1634–49.e17. Leoni G, D’Alise AM, Cotugno G, Langone F, Garzia I, De Lucia M, et al. A genetic vaccine encoding shared cancer neoantigens to treat tumors with microsatellite instability. Cancer Res. 2020 Sep 15;80(18):3972–82. Zaaimi Y, Aparicio T, Laurent-Puig P, Taieb J, Zaanan A. Advanced small bowel adenocarcinoma: molecular characteristics and therapeutic perspectives. Clin Res Hepatol Gastroenterol. 2016 Apr;40(2):154–60. Raghav K, Overman MJ. Small bowel adenocarcinomas: existing evidence and evolving paradigms. Nat Rev Clin Oncol. 2013 Sep;10(9):534–44. Huffman BM, Jin Z, Yadav S, Patel S, Nagorney DM, Truty MJ, et al. Novel prognostic factors in resected small bowel adenocarcinoma. Clin Colorectal Cancer. 2019 Sep;18(3):218–25. Ocasio Quinones GA, Woolf A. Small bowel cancer. Treasure Island, FL: StatPearls Publishing Copyright©, StatPearls Publishing LLC.; 2021. Morihiro T, Kuroda S, Kanaya N, Kakiuchi Y, Kubota T, Aoyama K, et al. PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer. Sci Rep. 2019 Mar 15;9(1):4633. Fu X, Liu Z, Xiang L, Liu M, Zheng X, Wang J, et al. PD-L1 predicts poor prognosis in surgically resected limited stage small-cell lung cancer. Cancer Manag Res. 2020;12:10939–48. Zhou QH, Li KW, Chen X, He HX, Peng SM, Peng SR, et al. HHLA2 and PD-L1 co-expression predicts poor prognosis in patients with clear cell renal cell carcinoma. J Immunother Cancer. 2020 Jan:8(1):e000157. Dai X, Pi G, Yang SL, Chen GG, Liu LP, Dong HH. Association of PD-L1 and HIF-1α coexpression with poor prognosis in hepatocellular carcinoma. Transl Oncol. 2018 Apr;11(2):559–66. Bonanno L, Pavan A, Dieci MV, Di Liso E, Schiavon M, Comacchio G, et al. The role of immune microenvironment in small-cell lung cancer: distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes. Eur J Cancer. 2018 Sep;101:191–200. Noh BJ, Hong SM, Jun SY, Eom DW. Prognostic implications of immune classification in a multicentre cohort of patients with small intestinal adenocarcinoma. Pathology. 2020 Feb;52(2):228–35. Article / Publication Details

First-Page Preview

Abstract of Clinical Study

Received: August 27, 2021
Accepted: September 19, 2021
Published online: March 29, 2022

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 5

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Copyright / Drug Dosage / Disclaimer Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

留言 (0)

沒有登入
gif