Table 1 Summary of included studies
Author | Study year | Country | Selection | Initial tumor screen | Number of participants | Proportion of positive IHC | Proportion of positive MSI | Proportion of negative methylation after positive tumor triage | Proportion of positive germline samples after positive tumor-based triage | Comments |
|---|---|---|---|---|---|---|---|---|---|---|
Backes et al.26 | 2009 | USA | None | IHC | 385 | 0.12 | NA | NA | 0.37 | IHC results not described by gene; MSI not clearly described |
Batte et al.14 | 2014 | USA | None | IHC | 579 | 0.07 | NA | NA | 0.8 | Only 36 tumors had MSH6 IHC testing; PMS2 not tested; 20 tumors were MSI-H; 37 were MSI-L |
Berends et al.27 | 2003 | USA | <50 years | IHC and MSI | 58 | 0.49 | 0.35 | NA | 0.09 | None |
Bruegl et al.28 | 2014 | USA | None | IHC | 412 | 0.29 | NA | 0.11 | NA | Only one MS region investigated; only MLH1 and MSH2 IHC carried out; results quoted in the paper are not consistent |
Buchanan et al.29 | 2013 | Australia | None | IHC | 702 | 0.24 | NA | 0.09 | 0.14 | Not clear how IHC was applied |
Buttin et al.30 | 2004 | USA | None | MSI | 413 | NA | 0.27 | 0.19 | NA | None |
Catasus et al.31 | 1998 | Spain | None | MSI | 42 | NA | 0.29 | NA | NA | PMS2 germline testing not performed; all MSI had GL |
Chadwick et al.32 | 2001 | USA | None | MSI | 74 | NA | 0.23 | NA | 0.12 | None |
Cook et al.33 | 2013 | Canada | <80 years | MSI | 480 | NA | 0.27 | NA | NA | Analysis includes 2 known LS carriers |
Cossio et al.34 | 2010 | Brazil | <50 years of strong FHx | IHC and MSI | 30 | 0.33 | 0.23 | NA | NA | None |
Dillon et al.13 | 2017 | USA | None | IHC | 233 | 0.26 | NA | 0.05 | 0.45 | None |
Djordjevic et al.35 | 2013 | USA | None | IHC | 154 | 0.30 | NA | 0.14 | NA | None |
Egoavil et al.36 | 2013 | Spain | None | IHC and MSI | 173 | 0.34 | 0.27 | 0.14 | 0.42 | 89 had unselected GL analysis; 4 GL results not available; those MSI +ve or MLH1 deficient without FHx did not have GL analysis; numbers of IHC MLH1 loss not clear |
Ferguson et al.37 | 2014 | Canada | None | IHC and MSI | 119 | 0.29 | 0.23 | NA | 0.08 | A pre universal screening cohort, described in this paper, was not included in this analysis; those who underwent testing not as a result of universal screening were also excluded |
Frolova et al.15 | 2015 | USA | None | IHC | 234 | 0.22 | NA | 0.09 | 0.31 | None |
Garg et al.38 | 2009 | USA | <50 years or LS morphology | IHC | 71 | 0.45 | NA | NA | NA | PMS2 not tested |
González et al.39 | 2012 | Puerto Rico | None | IHC | 20 | 0.25 | NA | NA | NA | None |
Goodfellow et al.40 | 2015 | USA | Endometrioid only | IHC and MSI | 1002 | 0.36 | 0.30 | 0.11 | 0.4 | Not all variants detected could be classified as pathogenic |
Hampel et al.41 | 2006 | USA | None | MSI | 543 | 0.34 | 0.22 | 0.06 | 0.02 | Germline pathogenic variants are not described; the PMS2 deficient case on IHC also lacked MSH6 expression |
Hartnett et al.42 | 2015 | USA | None | IHC | 205 | 0.21 | NA | 0.03 | 0.01 | Of the 24 tumors tested 5 did not have sufficient material for any MSI; a further 4 had sufficient material for limited analysis |
Hewitt et al.43 | 2006 | UK | FHx | MSI | 17 | 0.18 | NA | NA | None | |
Joehlin-Price et al.44 | 2014 | USA | None | IHC | 1054 | 0.22 | NA | NA | NA | None |
Kato et al.45 | 2016 | Japan | None | IHC | 360 | 0.03 | NA | 0.02 | 0.25 | Only PMS2 results clearly reported |
Kost et al.66 | 2016 | USA | <50 years | IHC | 83 | 0.24 | NA | 0.16 | None | |
Lee et al.46 | 2018 | Singapore | <50 years | IHC | 315 | 0.21 | NA | NA | NA | None |
Leenen et al.47 | 2012 | Netherlands | <70 years | IHC and MSI | 179 | 0.23 | 0.23 | 0.06 | 0.7 | Only MLH1 and MSH2 on IHC |
Lim et al.48 | 1996 | USA | None | MSI | 28 | NA | 0.32 | NA | NA | Two additional patients with previously known Lynch syndrome added to final results; only 3 germline results are clearly defined |
Lin et al.49 | 2016 | USA | Mixed | IHC | 76 | 0.22 | NA | 0.08 | 0.6 | 21 of 41 showed MSH2/MSH6 and 10 of 41 showed MLH1/PMS2; however authors also report individual protein loss consisting of 72 in total |
Long et al.66 | 2014 | China | None | IHC | 173 | 0.24 | NA | NA | NA | PMS2 not tested |
Lu et al.50 | 2007 | USA | <50 years | GL | 100 | 0.34 | 0.33 | 0.22 | 0.09 | None |
Chu et al.68 | 2015 | Hong Kong | <45 years | IHC | 67 | 0.33 | 0.23 | NA | None | |
Mas-Moya et al.17 | 2015 | USA | None | IHC | 215 | 0.33 | NA | 0.17 | 0.65 | Only those with IHC loss had MSI |
Matthews et al.51 | 2008 | USA | <50 years | IHC | 61 | 0.34 | 0.34 | NA | NA | MMR IHC done on TMA |
McConechy et al.52 | 2015 | Canada | None | MSI | 89 | NA | 0.26 | NA | NA | MSI results are not clear |
Mills et al.53 | 2014 | USA | None | IHC and MSI | 604 | 0.25 | NA | 0.09 | 0.81 | Three phases of testing using different tests and referral criteria; 4 had multiple gene loss on IHC; methylation testing not universally applied and therefore cannot make any sensible deductions from it |
Moline et al.54 | 2013 | USA | Mixed | IHC or MSI or IHC with Methylation | 245 | 0.25 | 0.13 | NA | 0.24 | None |
Najdawi et al.69 | 2017 | Australia | None | IHC | 124 | 0.24 | NA | NA | 0.33 | Only 9 of 11 of the Lynch-like tumors had germline testing |
Parc et al.55 | 2000 | USA | <52 years | IHC and MSI | 62 | 0.24 | 0.34 | NA | NA | MSH2 and MSH6 IHC outcomes not reported |
Pecorino et al.56 | 2017 | Italy | <50 years | IHC | 41 | 0.31 | 0.42 | NA | NA | None |
Pennington et al.70 | 2013 | USA | Serous only | GL | 151 | NA | NA | NA | 0.00 | One subject with < 10% serous histology had a MSH6 pathogenic variant |
Rabban et al.18 | 2014 | USA | >50 years | IHC | 273 | 0.15 | NA | 0.04 | 0.29 | None |
Resnick et al.57 | 2009 | USA | None | IHC | 477 | 0.28 | NA | NA | NA | None |
Riggi et al.58 | 2016 | Argentina | None | IHC | 84 | 0.33 | NA | NA | NA | None |
Ring et al.71 | 2013 | USA | <50 years | IHC | 111 | 0.26 | NA | NA | NA | None |
Ring et al.59 | 2016 | USA | None | IHC or MSI or IHC with methylation | 381 | NK | NK | NK | 0.06 | Tumor-based molecular triage was used but the results are not detailed |
Rubio et al.60 | 2016 | Spain | None | IHC and MSI | 94 | 0.33 | 0.27 | NA | 0.15 | GL result not clear |
Sugawara et al.61 | 2015 | Japan | AFP criteria | IHC | 182 | 0.30 | NA | 0.22 | NA | Of all samples 55% not tested |
Tan et al.65 | 2013 | Australia | <80 years | IHC | 246 | 0.24 | NA | NA | NA | None |
Walsh et al.62 | 2008 | Australia | <50 years | IHC and MSI | 146 | 0.26 | 0.35 | 0.18 | NA | None |
Watkins et al.73 | 2016 | USA | None | IHC | 242 | 0.20 | NA | 0.05 | 0.4 | None |
Woo et al.72 | 2014 | Malaya | Endometrioid only | IHC | 77 | 0.19 | NA | NA | NA | PMS2 not tested |
Yoon et al.63 | 2007 | Korea | None | IHC and MSI | 113 | 0.23 | 0.44 | 0.17 | 0.04 | None |
Zauber et al.64 | 2010 | USA | None | MSI | 213 | NA | 0.26 | 0.09 | NA | None |
