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. D. repair deficiency tumors with a mutation and sensitivity to DNA 2014; PubMed Scopus Google Scholar The Idylla MSI test tissue from CRC from which are by a of and the seven are with The were detected from the or with The the of the a a for valid This MSI the of a or biomarker is and as mutation mutation or The MSI status of a can be with at least five be the MSI status of the is The of at least two markers result in the status the status is as microsatellite is by this The Idylla MSI test the from to reporting of microsatellite the Idylla MSI a tissue of and a tissue of were used with a slide of and a of and a of were used with a slide of this of one to five were used an invalid test result was the test was with the tissue The test was performed as the for use of the In this study, the Idylla MSI assay was because the in Idylla MSI test was on the The Promega MSI Analysis System version five mononucleotide markers and two markers The assay for of DNA by In this study, three tissue of to were a tumor of at least was was performed to DNA was performed on a the DNA to the of the the was with a the the was to in Promega MSI analysis was performed to the of the with of as This has been at for routine use to the for with the of the and of tissue were to the performance of the the a was and for the an was were with the version were MSI-H two or more mononucleotide markers of five were In all five markers be evaluated and than four markers were evaluated as the test was and one repeat test was a a of was to the expression of four MMR IHC analysis was performed on the for samples and and on a and for samples to The were used for this PMS2 and IHC were performed the for at and the detection system of The was for on the and for in with a on the the was for on the and the to use was for in with a on the and the and the PMS2 was for on the and for in with a on the IHC for MSI evaluation was performed on the for samples and and to that on the The and were used on the and PMS2 in with the at and detection system of the and PMS2 were used in with the for and and for the IHC for the four MMR markers were to use to were to loss of MMR function loss of expression of and PMS2 or loss of and expression was observed. with the sole loss of PMS2 and were for MMR-deficient with the sole loss of or were to be of MMR status this is more due to loss of expression of MMR proteins were to have an MMR the the IHC analysis was the Tumor was used with the System and the System the of the In of were used of the was the was to and a with of was and on an the System and the Analysis was performed in version the Tumor samples with of with the for the were to or 15% of The analysis of samples were valid the of with was with to were to have a low samples with to were to have a and samples with were to have a The is as with MSI-H or status as by the test MSI analysis or IHC The were with the Idylla MSI test and assay with the Idylla MSI test and with the with the Idylla MSI test and with the and with the Idylla MSI test and with the of the discordant cases with the of of of tumor were by the version was as the performance of the Idylla MSI 330 CRC samples two testing were the of at least tumor and the of at least tissue from one to five tissue or at least tissue from one to five tissue In of the tumor tissue was to the tumor In the majority of cases tissue from the was and are in the 330 patients, were and were with a of the and and invalid with Promega with IHC of to of tumor in tissue used for analysis of the tissue tissue slide in a the 330 was for and were stage stage stage and stage on the of was on the of the and In the majority of the of was 5% of the tumor tissue cases with a of to a valid MSI result with the Idylla MSI test. tissue were used in this the of the was tissue than a valid result with the Idylla MSI that the test can samples. and CRC tissue samples were with the Promega MSI Analysis System and the Idylla MSI test on samples a test it was to that have the samples to be for the Promega MSI only three samples for the Idylla MSI test In seven samples invalid results with the Promega MSI analysis two of an invalid result with the Idylla MSI test The seven invalid samples were for the analysis of with Idylla MSI and Promega MSI in a the results of the Idylla MSI test were compared with the Promega MSI the for status the Idylla MSI test and the Promega MSI The was The was and the was discordant was This was invalid by Promega MSI and MSI-H mononucleotide the Idylla MSI seven the seven of this from the an MSI-H result with the Idylla MSI test of the seven biomarkers the samples with MSI-H a analysis of the number of markers for assay is in Idylla MSI and Promega MSI this was also MSI-H with the Idylla MSI microsatellite microsatellite this was also MSI-H with the Idylla MSI in a of with Idylla MSI and Promega MSI Analysis for the MSI-H microsatellite microsatellite in a microsatellite microsatellite microsatellite microsatellite all the 330 samples for Idylla MSI test historical IHC data for and expression were two the IHC results were invalid because at least one MMR expression marker to be were detected by evaluating or the cases a valid result with the Idylla MSI of with Idylla MSI and and for MMR for MMR deficiency because sole loss of PMS2 or was observed, MMR status because sole loss of or was MMR for MMR deficiency because sole loss of PMS2 or was observed, MMR status because sole loss of or was is as at least one of the four markers expression in the tissue DNA mismatch repair protein DNA mismatch DNA mismatch repair protein DNA mismatch repair protein mismatch repair endonuclease for MMR deficiency because sole loss of PMS2 or was observed, MMR status because sole loss of or was observed. in a is as at least one of the four markers expression in the tissue DNA mismatch repair protein DNA mismatch DNA mismatch repair protein DNA mismatch repair protein mismatch repair endonuclease IHC evaluation of and in an MMR status for seven cases because the sole loss of or expression was observed. cases were for MMR deficiency because the sole loss of PMS2 and expression was and the Idylla MSI a valid result was in all of the samples for MMR deficiency and three of the seven samples with MMR status The Promega MSI analysis Analysis of the MMR in the or by for MMR MMR DNA mismatch repair protein DNA mismatch DNA mismatch repair protein DNA mismatch repair protein microsatellite microsatellite mismatch repair endonuclease for MMR MMR in a DNA mismatch repair protein DNA mismatch DNA mismatch repair protein DNA mismatch repair protein microsatellite microsatellite mismatch repair endonuclease the the Idylla MSI test and the historical IHC data, samples were samples with an invalid IHC result, samples with an or IHC and cases with an invalid Idylla MSI test The was The was and the was In four discordant cases were In the of the IHC loss of MMR function, the Idylla MSI test In one of loss of and expression was in the three loss of and PMS2 was of the IHC of the discordant cases that the loss of and PMS2 expression in samples and was and to of tumor with Idylla MSI and IHC function DNA mismatch microsatellite microsatellite in a Analysis of the Analysis in to the and Promega MSI Analysis this was also MSI-H with the Idylla MSI of the IHC slide loss of DNA mismatch repair protein DNA mismatch DNA mismatch repair protein DNA mismatch repair protein microsatellite microsatellite mismatch repair endonuclease tumor mutation this was also MSI-H with the Idylla MSI in a DNA mismatch microsatellite microsatellite of the IHC slide loss of DNA mismatch repair protein DNA mismatch DNA mismatch repair protein DNA mismatch repair protein microsatellite microsatellite mismatch repair endonuclease tumor mutation IHC and Idylla MSI test four discordant cases were cases all loss of MMR expression were to the Idylla MSI test. of the four cases were also to the Promega MSI analysis of the discordant samples with of the of of tumor be detected the of a in the DNA MMR in the was the of detected by the Tumor one the was a in the DNA repair In this the result with the initial Idylla MSI test result and were in with the IHC Promega MSI In the three the was of an DNA MMR for the majority of the results were in with the Idylla MSI test results In this study, the performance of the Idylla MSI a fast and test to the microsatellite status on of CRC patients, was Compared with the Promega MSI an of 99.7%, a of 98.7%, and an of was with the Idylla MSI test. results are in with the of B. Van J. E. L. K. T. G. L. A. L. R. M. H. D. K. E. of microsatellite instability in colorectal cancer samples with a of markers by of the Idylla MSI test Clin Oncol. Google Scholar the Idylla MSI test discordant was from the an MSI-H result with the Idylla test and an invalid result with the Promega be at the of this initial Alternatively, a in tumor be the of because the was in the to be performed to the tumor The Idylla MSI test seven markers, and the Promega test five markers. that three or more markers were with in the majority of cases with MSI-H with Idylla compared with with of the 330 samples seven cases an invalid result with the Promega MSI and two cases an invalid result with the Idylla MSI test The Idylla MSI test is with DNA from because it has been to The low of invalid results that the Idylla MSI test can with as a of of and tissue The Idylla MSI test compared with the Promega MSI is to and and a of is because the assay <2.5 hours. the Idylla MSI test a of and is to This was the repeat testing performed in this only one of the three initial invalid Idylla MSI test results of of the initial invalid Promega MSI analysis results of valid to the for the Idylla MSI test a tissue of the Promega at least of This that the Promega is more for samples with as samples and In this study, samples of an invalid result with the Idylla MSI test. The Promega test also an invalid result for more study with is to test which assay is better for In to the Promega MSI the Idylla MSI test a analysis of of this study is that were with the Promega MSI This can to an of markers as In specimens with as colorectal is always Compared with the IHC data, an of 98.7%, a of 94.4%, and an of were with the Idylla MSI test. two valid be from the IHC In a valid Idylla MSI test result be the two cases with invalid Idylla MSI test results valid results with Consequently, IHC is a in the cases where the Idylla MSI test and MSI-H status is generally loss of expression of the and PMS2 or of the and is observed. the sole loss of one marker can in cases of Lynch syndrome that In this study, cases loss of one mismatch protein and two cases the loss of an of markers, and or and cases the Idylla MSI test a valid cases were as and cases were as Promega MSI analysis Consequently, samples with loss of one MMR expression marker always The Idylla MSI test can as an the IHC data are to be that cases of Lynch syndrome with this is mononucleotide markers are used for MSI M.J. 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
Zwaenepoel et al. (Tue,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: