Skip to main content
SpringerLink
Log in

Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Determination of microsatellite instability (MSI) and mismatch repair deficiency (MMRD), respectively, in endometrial carcinomas (ECs) is important for diagnostic and prognostic purposes, identification of Lynch syndrome carriers, and selection of patients for immunotherapy. The Idylla™ MSI assay is fully automated, does not require non-tumoral tissue, and can be performed in about 150 min. Two hundred forty-two formalin-fixed paraffin-embedded (FFPE) EC samples from 7 international centers were tested by the Idylla™ MSI assay and compared to the Promega™ MSI Analysis System and immunohistochemistry (IHC) for MMR proteins. The cases were selected with an enrichment of MSI EC to around 40%. Concordance was 87.5% between the Idylla™ MSI assay and IHC and 88.58% between IHC and Promega™ MSI assay. Concordance between Idylla™ and Promega™ MSI assays was 89.91%. Discordant results occurred more frequently in cases with MSH6 or PMS2 deficiency. Invalid cases occurred with the three techniques (IHC, 7.00%; Promega™ MSI assay, 5.37%; and Idylla™ MSI assay, 2.47%). The concordance rate between Idylla™ MSI assay and the other 2 methods increased to 88.83% for IHC and to 91.22% for the Promega™ MSI assay when the cutoff of instability in the scoring system was moved from 0.5 to 0.3. The Idylla™ MSI assay is a rapid and highly concordant test for MSI in EC. Modification of the Idylla™ scoring system could increase the sensitivity and specificity of the MSI assay for EC analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Matias-Guiu X, Prat J (2013) Molecular pathology of endometrial carcinoma. Histopathology 62:111–123

    Article  Google Scholar 

  2. Hampel H, Pearlman R, de la Chapelle A, Pritchard CC, Zhao W, Jones D et al (2021) Double somatic mismatch repair gene pathogenic variants as common as Lynch syndrome among endometrial cancer patients. Gynecol Oncol 160:161–168

    Article  CAS  Google Scholar 

  3. Broaddus RR, Lynch HT, Chen LM, Daniels MS, Conrad P, Munsell MF et al (2006) Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 106:87–94

    Article  CAS  Google Scholar 

  4. Honore LH, Hanson J, Andrew SE (2006) Microsatellite instability in endometrioid endometrial carcinoma: correlation with clinically relevant pathologic variables. Int J Gynecol Cancer 16:1386–1392

    Article  CAS  Google Scholar 

  5. Shia J, Black D, Hummer AJ, Boyd J, Soslow RA (2008) Routinely assessed morphological features correlate with microsatellite instability status in endometrial cancer. Hum Pathol 39:116–125

    Article  CAS  Google Scholar 

  6. Luis A. Diaz, Jennifer N. Uram, Hao Wang, Bjarne Bartlett, Holly Kemberling, Aleksandra Eyring, Nilofer Saba Azad, Tianna Dauses, Dan Laheru, James J. Lee, Todd S. Crocenzi, Richard M. Goldberg, George A. Fisher, Tim F. Greten, Christian Frederick Meyer, Amanda Nickles Fader, Deborah Kay Armstrong, Minori Koshiji, Bert Vogelstein, Dung T. Le (2016). Programmed death-1 blockade in mismatch repair deficient cancer independent of tumour histology. J Clin Oncol 34:15_suppl, 3003–3003.

  7. Ott PA, Bang Y-J, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS et al (2016) Pembrolizumab in advanced endometrial cancer: preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol 34(15_ suppl):5581

    Article  Google Scholar 

  8. The Cancer Genome Atlas Research Network (2013) Integrated genomic characterization of endometrial carcinoma. Nature 497:67–73

    Article  Google Scholar 

  9. Piulats JM, Guerra E, Gil-Martín M, Roman-Canal B, Gatius S, Sanz-Pamplona R et al (2017) Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol 145:200–207

    Article  CAS  Google Scholar 

  10. Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N et al (2015) A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer 113:299–310

    Article  CAS  Google Scholar 

  11. Vermij L, Smit V, Nout R, Bosse T (2020) Incorporation of molecular characteristics into endometrial cancer management. Histopathology 76:52–63

    Article  Google Scholar 

  12. León-Castillo A, Britton H, McConechy MK, McAlpine JN, Nout R, Kommoss S et al (2020) Interpretation of somatic POLE mutations in endometrial carcinoma. J Pathol 250:323–335

    Article  Google Scholar 

  13. Modica I, Soslow RA, Black D, Tornos C, Kauff N, Shia J (2007) Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma. Am J Surg Pathol 31:744–751

    Article  Google Scholar 

  14. Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S et al (2021) ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer 154:327–353

    Google Scholar 

  15. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J et al (2004) Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 96:261–268

    Article  CAS  Google Scholar 

  16. Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T et al (2019) ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol 30:1232–1243

    Article  CAS  Google Scholar 

  17. Hampel H, Pearlman R, Beightol M, Zhao W, Jones D, Frankel WL et al (2018) Assessment of tumour sequencing as a replacement for Lynch syndrome screening and current molecular tests for patients with colorectal cancer. JAMA Oncol 4:806–813

    Article  Google Scholar 

  18. Hissong E, Crowe EP, Yantiss RK, Chen YT (2018) Assessing colorectal cancer mismatch repair status in the modern era: a survey of current practices and re-evaluation of the role of microsatellite instability testing. Mod Pathol 4:806–813

    Google Scholar 

  19. Middha S, Zhang L, Nafa K, Jayakumaran G, Wong D, Kim HR et al (2018) Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data. JCO Precis Oncol. https://doi.org/10.1200/PO.17.00084

    Article  Google Scholar 

  20. Shia J (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: part I. The utility of immunohistochemistry. J Mol Diagnostics 10:293–300

    Article  Google Scholar 

  21. Zhao H, Thienpont B, Yesilyurt BT, Moisse M, Reumers J, Coenegrachts L et al (2014) Mismatch repair deficiency endows tumours with a unique mutation signature and sensitivity to DNA double-strand breaks. Elife 3:02725

    Google Scholar 

  22. Li X, Xu J, Li L, Mu X, Wang Y, Li X (2019) Evaluation of a fully automated Idylla test system for microsatellite instability in colorectal cancer. Clin Colorectal Cancer. 18:316–323

    Article  Google Scholar 

  23. Lee M, Chun SM, Sung CO, Kim SY, Kim TW, Jang SJ et al (2019) Clinical utility of a fully automated microsatellite instability test with minimal hands-on time. J Pathol Transl Med 53:386–392

    Article  Google Scholar 

  24. Zwaenepoel K, Holmgaard Duelund J, De Winne K, Maes V, Weyn C, Lambin S et al (2020) Clinical performance of the Idylla MSI test for a rapid assessment of the DNA microsatellite status in human colorectal cancer. J Mol Diagnostics 22:386–395

    Article  CAS  Google Scholar 

  25. Samaison L, Grall M, Staroz F, Uguen A (2019) Microsatellite instability diagnosis using the fully automated Idylla platform: feasibility study of an in-house rapid molecular testing ancillary to immunohistochemistry in pathology laboratories. J Clin Pathol 72:830–835

    Article  CAS  Google Scholar 

  26. De Craene B, Van de Velde J, Bellon E, Gazin M, Rondelez E, Vandenbroeck L et al (2018) Detection of microsatellite instability (MSI) with a novel set of 7 Idylla biomarkers on colorectal cancer samples in a multi-center study. Ann Oncol 29(Supplement):8

    Google Scholar 

  27. Ukkola I, Nummela P, Pasanen A, Kero M, Lepistö A, Kytölä S et al (2021) Detection of microsatellite instability with Idylla™ MSI assay in colorectal and endometrial cancer. Virchows Arch. https://doi.org/10.1007/s00428-021-03082-w

    Article  PubMed  PubMed Central  Google Scholar 

  28. Siemanowski J, Schömig-Markiefka B, Buhl T, Haak A, Siebolts U, Dietmaier W, Arens N, Pauly N, Ataseven B, Büttner R, Merkelbach-Bruse S (2021) Managing difficulties of microsatellite instability testing in endometrial cancer-limitations and advantages of four different PCR-based approaches. Cancers (Basel) 13:1268

    Article  CAS  Google Scholar 

  29. Gilson P, Levy J, Rouyer M, Demange J, Husson M, Bonnet C, Salleron J, Leroux A, Merlin JL, Harlé A (2020) Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers. Sci Rep 10:16386

    Article  Google Scholar 

  30. Pécriaux A, Favre L, Calderaro J, Charpy C, Derman J, Pujals A (2021) Detection of microsatellite instability in a panel of solid tumours with the Idylla MSI Test using extracted DNA. J Clin Pathol 74:36–42

    Article  Google Scholar 

  31. Dedeurwaerdere F, Claes KB, Van Dorpe J, Rottiers I, Van der Meulen J, Breyne J, Swaerts K, Martens G (2021) Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer. Sci Rep 11:12880

    Article  CAS  Google Scholar 

  32. Hause RJ, Pritchard CC, Shendure J, Salipante SJ (2016) Classification and characterization of microsatellite instability across 18 cancer types. Nat Med 22:1342–1350

    Article  CAS  Google Scholar 

  33. Wang Y, Shi C, Eisenberg R, Vnencak-Jones CL (2017) Differences in microsatellite instability profiles between endometrioid and colorectal cancers: a potential cause for false-negative results? J Mol Diagnostics 19:57–64

    Article  Google Scholar 

  34. Wu X, Snir O, Rottmann D, Wong S, Buza N, Hui P (2019) Minimal microsatellite shift in microsatellite instability high endometrial cancer: a significant pitfall in diagnostic interpretation. Mod Pathol 32:650–658

    Article  CAS  Google Scholar 

  35. Kuismanen SA, Moisio AL, Schweizer P, Truninger K, Salovaara R, Arola J et al (2002) Endometrial and colorectal tumours from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Am J Pathol 160:1953–1958

    Article  CAS  Google Scholar 

Download references

Funding

Work supported by Grupos Estables Asociación Española contra el Cancer. Tumors were managed through the Xarxa de Bancs de Tumors de Catalunya (XBTC IRBLleida BIOBANK (B.0000682)), as well as Plataforma de Bionacos IRBLLEIDA and IDIBELL (PT 20/0021) and PT(20/0171). Cartridges were provided free of charge by Idylla.

Author information

Authors and Affiliations

  1. Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLleida, CIBERONC, Av Rovira Roure, 80, 25198, Lleida, Spain

    Sonia Gatius, Ana Velasco & Xavier Matias-Guiu

  2. Hospital Universitari de Bellvitge, Universitat de Barcelona, IDIBELL, CIBERONC, Barcelona, Spain

    Mar Varela & Xavier Matias-Guiu

  3. Pathology Department, CDB, Hospital Clinic, Barcelona, Universitat de Barcelona, IDIBAPS, CIBEREHD, Barcelona, Spain

    Miriam Cuatrecasas & Pedro Jares

  4. Department of Pathology, General Hospital Graz II, Styrian Hospital Corporation and Medical University of Graz, Graz, Austria

    Lisa Setaffy, Sabrina Croce & Sigurd Lax

  5. Département de Biopathologie, Institut Bergonié, Bordeaux, France

    Benjamin Bonhomme

  6. Hospital Ramon Y Cajal, IRYCIS, CIBERONC, Madrid, Spain

    Almudena Santon & Jose Palacios

  7. Department of Gynecologic Oncology, Division of Cancer Medicine, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway

    Kristina Lindemann

  8. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0316, Oslo, Norway

    Kristina Lindemann & Ben Davidson

  9. Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, 0310, Oslo, Norway

    Ben Davidson

  10. School of Medicine, Johannes Kepler University, Linz, Austria

    Sigurd Lax

  11. Faculty of Medicine, University of Alcalá, Madrid, Spain

    Jose Palacios

Authors
  1. Sonia Gatius
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Velasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mar Varela
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miriam Cuatrecasas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pedro Jares
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lisa Setaffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Benjamin Bonhomme
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Almudena Santon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kristina Lindemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sabrina Croce
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ben Davidson
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sigurd Lax
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jose Palacios
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Xavier Matias-Guiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SG collected the samples, analyzed the data, participated in the study design, and wrote, edited, and reviewed the manuscript.

AV participated in the study design, assisted in carrying out experiments, and reviewed the manuscript.

MV participated in the study design, assisted in carrying out experiments, and reviewed the manuscript.

MC collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

PJ collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

LS collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

BB collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

AS collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

KL collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

SC collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

BD collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

SL collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

JP collected the samples, assisted in carrying out experiments, participated in the study design, and reviewed the manuscript.

XMG conceived and designed the study and edited and reviewed the manuscript.

Corresponding author

Correspondence to Sonia Gatius.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

The study was approved by local Ethics Committees, according to the Declaration of Helsinki.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gatius, S., Velasco, A., Varela, M. et al. Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study. Virchows Arch 480, 1031–1039 (2022). https://doi.org/10.1007/s00428-022-03291-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-022-03291-x

Keywords

Search

Navigation