Key points are not available for this paper at this time.
In this study, the clinical performance of the Idylla MSI test (investigational use only) was evaluated in 330 colorectal carcinoma samples (all stages). This test is fully automated, from formalin-fixed, paraffin-embedded slide to result, and gives a result in <2.5 hours. Compared with the Promega MSI Analysis System version 1.2, an overall agreement, sensitivity, and specificity of 99.7%, 98.7%, and 100%, respectively, was reached. Whereas seven samples were invalid with the Promega MSI Analysis System, only two were invalid with the Idylla MSI test. Compared with the historical immunohistochemistry (IHC) data, overall agreement, sensitivity, and specificity of 98.7%, 94.4%, and 100%, respectively, were observed. Tumor mutation burden analysis of the discordant IHC cases was in favor of the Idylla MSI test result in three of the four samples. Furthermore, for those cases where the IHC data were invalid or hard to interpret because sole loss of one DNA mismatch repair deficiency marker was observed, Idylla MSI test results were always valid and accurate. Herein, the Idylla MSI test has been shown to be an accurate, fast screening assay for the detection of microsatellite status in colorectal cancer patients, with a low number of invalid results. In this study, the clinical performance of the Idylla MSI test (investigational use only) was evaluated in 330 colorectal carcinoma samples (all stages). This test is fully automated, from formalin-fixed, paraffin-embedded slide to result, and gives a result in <2.5 hours. Compared with the Promega MSI Analysis System version 1.2, an overall agreement, sensitivity, and specificity of 99.7%, 98.7%, and 100%, respectively, was reached. Whereas seven samples were invalid with the Promega MSI Analysis System, only two were invalid with the Idylla MSI test. Compared with the historical immunohistochemistry (IHC) data, overall agreement, sensitivity, and specificity of 98.7%, 94.4%, and 100%, respectively, were observed. Tumor mutation burden analysis of the discordant IHC cases was in favor of the Idylla MSI test result in three of the four samples. Furthermore, for those cases where the IHC data were invalid or hard to interpret because sole loss of one DNA mismatch repair deficiency marker was observed, Idylla MSI test results were always valid and accurate. Herein, the Idylla MSI test has been shown to be an accurate, fast screening assay for the detection of microsatellite status in colorectal cancer patients, with a low number of invalid results. Colorectal cancer (CRC) is the third most common cancer in men and the second in women. Although the majority of CRC cases are sporadic in nature, 5% to 10% of cases are due to inherited autosomal dominant mutations. The most common subtype of hereditary CRC is Lynch syndrome (hereditary nonpolyposis colon cancer), which accounts for approximately 3% to 5% of all CRC diagnoses.1Lynch H.T. Snyder C.L. Shaw T.G. Heinen C.D. Hitchins M.P. Milestones of Lynch syndrome: 1895-2015.Nat Rev Cancer. 2015; 15: 181-194Crossref PubMed Scopus (457) Google Scholar,2Yamamoto H. Imai K. Microsatellite instability: an update.Arch Toxicol. 2015; 89: 899-921Crossref PubMed Scopus (132) Google Scholar Consequently, it is imperative that patients with CRC be screened for Lynch syndrome. Approximately 15% of the CRC samples exhibit loss of DNA mismatch repair (MMR) function, and in about one third of this population, the tumor development is associated with Lynch syndrome.3de la Chapelle A. Hampel H. Clinical relevance of microsatellite instability in colorectal cancer.J Clin Oncol. 2010; 28: 3380-3387Crossref PubMed Scopus (240) Google Scholar Consequently, loss of MMR function is used as an initial screening marker to identify patients with Lynch syndrome. Investigating the MMR status in CRC also has prognostic value. Patients with MMR-deficient tumors generally have a better survival. Furthermore, MMR-deficient tumors have been associated with an apparent resistance to treatment with 5-fluorouracil therapy.4Roth A.D. Tejpar S. Delorenzi M. Yan P. Fiocca R. Klingbiel D. Dietrich D. Biesmans B. Bodoky G. Barone C. Aranda E. Nordlinger B. Cisar L. Labianca R. Cunningham D. Van Cutsem E. Bosman F. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.J Clin Oncol. 2010; 28: 466-474Crossref PubMed Scopus (932) Google Scholar,5Sinicrope F.A. Sargent D.J. Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications.Clin Cancer Res. 2012; 18: 1506-1512Crossref PubMed Scopus (192) Google Scholar Loss of MMR function leads to microsatellite instability–high (MSI-H) status and can be detected by evaluating the tumor tissue expression of the MMR proteins DNA mismatch repair protein Mlh1 (MLH1), mismatch repair endonuclease PMS2 (PMS2), DNA mismatch repair protein Msh2 (MSH2), and DNA mismatch repair protein Msh6 (MSH6).6Shia J. 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 Diagn. 2008; 10: 293-300Abstract Full Text Full Text PDF PubMed Scopus (473) Google Scholar Alternatively, MSI-H status can be evaluated on tumor DNA.7Zhang L. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part II. The utility of microsatellite instability testing.J Mol Diagn. 2008; 10: 301-307Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar, 8Ryan E. Sheahan K. Creavin B. Mohan H.M. Winter D.C. The current value of determining the mismatch repair status of colorectal cancer: a rationale for routine testing.Crit Rev Oncol Hematol. 2017; 116: 38-57Crossref PubMed Scopus (76) Google Scholar, 9Sepulveda A.R. Hamilton S.R. Allegra C.J. Grody W. Cushman-Vokoun A.M. Funkhouser W.K. Kopetz S.E. Lieu C. Lindor N.M. Minsky B.D. Monzon F.A. Sargent D.J. Singh V.M. Willis J. Clark J. Colasacco C. Rumble R.B. Temple-Smolkin R. Ventura C.B. Nowak J.A. Molecular biomarkers for the evaluation of colorectal cancer: guideline summary from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology.J Oncol Pract. 2017; 13: 333-337Crossref PubMed Scopus (20) Google Scholar In general, this analysis is performed with at least five microsatellite markers, often mononucleotide or dinucleotide repeat markers. Because dinucleotide repeats have a lower sensitivity and specificity compared with mononucleotide repeats for identifying tumors with an MSI-H phenotype, the revised Bethesda Guidelines of the National Cancer Institute regarding MSI testing and Lynch syndrome advises the use of more than two mononucleotide markers in the evaluation of MSI.10Bartley A.N. Hamilton S.R. Alsabeh R. Ambinder E.P. Berman M. Collins E. Fitzgibbons P.L. Gress D.M. Nowak J.A. Samowitz W.S. Zafar S.Y. Members of the Cancer Biomarker Reporting Workgroup, College of American PathologistsTemplate for reporting results of biomarker testing of specimens from patients with carcinoma of the colon and rectum.Arch Pathol Lab Med. 2014; 138: 166-170Crossref PubMed Scopus (33) Google Scholar, 11Murphy K.M. Zhang S. Geiger T. Hafez M.J. Bacher J. Berg K.D. Eshleman J.R. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers.J Mol Diagn. 2006; 8: 305-311Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar, 12Zhao H. Thienpont B. Yesilyurt B.T. Moisse M. Reumers J. Coenegrachts L. Sagaert X. Schrauwen S. Smeets D. Matthijs G. Aerts S. J. A. A. F. D. repair deficiency tumors with a mutation and sensitivity to DNA 2014; PubMed Scopus Google Scholar, A. S. la Chapelle A. J. R. Lindor N.M. R. Hamilton S.R. J. A. Lynch H.T. P. A.N. S. Bethesda for hereditary nonpolyposis colorectal cancer and microsatellite Cancer PubMed Scopus Google Scholar on data on the of markers, the MSI Analysis System five mononucleotide markers that are Loss of MMR function leads to DNA in the tumor This of results in a tumor mutation burden and an expression of F. S. C. A. R. A.M. A. J. K. J. detection of mismatch repair deficiency in colorectal in Clin Oncol. PubMed Scopus Google Scholar, S.Y. J. burden and for detection of microsatellite instability in colorectal cancer by Mol Diagn. Full Text Full Text PDF PubMed Scopus Google Scholar, A. S. Tumor testing and for of mismatch repair PubMed Scopus Google Scholar the of as has been to the of tumor Consequently, the and has an to an for patients with MMR-deficient tumors as by MSI or MMR protein expression H. repair deficiency of tumors to 2017; PubMed Scopus Google H. H. A.D. A.D. D. B. A. la Chapelle A. M. F. T. D.M. S. Eshleman J.R. B. in tumors with Med. 2015; PubMed Scopus Google Scholar In this study, the performance of the Idylla MSI was This test is fully and can results from formalin-fixed, paraffin-embedded tissue hours. Compared with the Promega MSI Analysis System version 1.2, an overall sensitivity, and specificity of 99.7%, 98.7%, and 100%, respectively, were In the Idylla MSI test was compared with immunohistochemistry (IHC) loss of expression of the MMR overall sensitivity, and specificity of 98.7%, 94.4%, and 100%, respectively, were with MMR protein expression and the Idylla MSI test were by results were in with the Idylla MSI test results in the majority of the the data that the Idylla MSI test is a screening test to and identify the or of MSI-H in CRC This study was by the of the and clinical tumor samples from 330 CRC patients for and IHC and at least MSI-H samples in the study, a of MSI-H samples was The study was in two clinical the and the performed the analysis of microsatellite status by Idylla MSI test on to stage to CRC samples. Analysis of microsatellite status with the Promega MSI Analysis System version 1.2, was performed at for all samples. tissue of or were The and were with and on of and of the samples were by to a tumor of at least to five were with the Idylla MSI and three were used for the Promega MSI Analysis System version The Idylla MSI test is an in test for the detection of a panel of seven biomarkers for of microsatellite status in H. Thienpont B. Yesilyurt B.T. Moisse M. Reumers J. Coenegrachts L. Sagaert X. Schrauwen S. Smeets D. Matthijs G. Aerts S. J. A. A. F. 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A. C. A. A. R. with loss of expression are MSI-H screened with a of five mononucleotide Cancer. 2010; PubMed Scopus Google Scholar In with loss of IHC has been in the of or A.N. Hamilton S.R. Alsabeh R. Ambinder E.P. Berman M. Collins E. Fitzgibbons P.L. Gress D.M. Nowak J.A. Samowitz W.S. Zafar S.Y. Members of the Cancer Biomarker Reporting Workgroup, College of American PathologistsTemplate for reporting results of biomarker testing of specimens from patients with carcinoma of the colon and rectum.Arch Pathol Lab Med. 2014; 138: 166-170Crossref PubMed Scopus (33) Google Scholar In four a IHC data and Idylla MSI test data were observed. In one Promega MSI analysis the IHC result, for This also a tumor mutation that a of the DNA repair is In the three the Promega MSI analysis the result of the Idylla MSI test. The tumor mutation of three samples was of the IHC that the two cases with and PMS2 loss and loss of proteins and to data are in with that a loss in of the tumor with MMR function J. M. M. E. X. M. J. for DNA mismatch repair proteins in are PubMed Scopus Google L. for Lynch syndrome by immunohistochemistry of mismatch repair of result and with Pathol Lab Med. PubMed Scopus Google Scholar The with loss of and expression a mutation in the the discordant the National Cancer screening for MMR status by IHC or by D. S. D.J. T. J.A. G. D. W. Hamilton S.R. Hampel H. Lynch S.E. M. G. D. M. S. colorectal version clinical in PubMed Scopus Google Scholar IHC is often because it can be performed and the of four IHC is Although this was in this study, the that IHC results in 5% to of A.N. Hamilton S.R. Alsabeh R. Ambinder E.P. Berman M. Collins E. Fitzgibbons P.L. Gress D.M. Nowak J.A. Samowitz W.S. Zafar S.Y. Members of the Cancer Biomarker Reporting Workgroup, College of American PathologistsTemplate for reporting results of biomarker testing of specimens from patients with carcinoma of the colon and rectum.Arch Pathol Lab Med. 2014; 138: 166-170Crossref PubMed Scopus (33) Google H. Thienpont B. Yesilyurt B.T. Moisse M. Reumers J. Coenegrachts L. Sagaert X. Schrauwen S. Smeets D. Matthijs G. Aerts S. J. A. A. F. D. repair deficiency tumors with a mutation and sensitivity to DNA 2014; PubMed Scopus Google R. of cancer patients with Lynch syndrome: and in mismatch repair 2012; PubMed Scopus Google Scholar In this study, IHC results were observed. IHC is used as a for Lynch this is an because testing by a be the microsatellite status is used as a test for H. repair deficiency of tumors to 2017; PubMed Scopus Google H. H. A.D. A.D. D. B. A. la Chapelle A. M. F. T. D.M. S. Eshleman J.R. B. in tumors with Med. 2015; PubMed Scopus Google Scholar and a are Consequently, and results be the Idylla MSI one and two invalid results were observed. the IHC and or only results were observed. This study has been to MSI is also in about 15% of and and at lower in R. J. L. S. of microsatellite instability cancer Oncol. 2017; Google Scholar for has been for all patients with tumors MSI-H or MMR E. Sheahan K. Creavin B. Mohan H.M. Winter D.C. The current value of determining the mismatch repair status of colorectal cancer: a rationale for routine testing.Crit Rev Oncol Hematol. 2017; 116: 38-57Crossref PubMed Scopus (76) Google W. J. S. D. M.J. D.C. E. M. A. J. P. P. C.L. A. Analysis of the of microsatellite instability in cancer and to Oncol. PubMed Scopus Google Scholar that in the at can be and MSI is more to with a C. R. C.L. in microsatellite instability and colorectal a for Mol Diagn. 2017; Full Text Full Text PDF PubMed Scopus Google B. in evaluation of Lynch syndrome in patients with Pathol Full Text Full Text PDF PubMed Scopus Google Scholar data the clinical performance of the Idylla MSI test in tumors be evaluated as In the Idylla MSI test has been shown to be in identifying the microsatellite status in CRC samples. The test is fully and gives results hours. for with tissue for and all of in the historical IHC data and evaluating the
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