Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data

Guastadisegni, Cecilia; Colafranceschi, Mauro; Ottini, Laura; Dogliotti, Eugenia

doi:10.1016/j.ejca.2010.05.009

Cited by 346 publications

(307 citation statements)

References 76 publications

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“…Two systematic reviews and meta-analyses have indicated improved overall survival (OS) in patients with MSI CRC compared with MSS tumours (Guastadisegni et al, 2010;Popat et al, 2005). Popat et al, stratified survival in CRC patients depending on MMR status and found improved OS in MSI CRC versus MSS (Hazard ratio [HR] 0.65; 95% CI: 0.59-0.71; heterogeneity P = 0.16; I 2 = 20%).…”

Section: Universal Screeningmentioning

confidence: 99%

“…In prospectively col- (Andre et al, 2015;Gavin et al, 2013;Guastadisegni et al, 2010;Klingbiel et al, 2015;Popat et al, 2005;Roth et al, 2012;Sinicrope et al, 2015). lected tumor tissue MSI was detected in 314 of 2580 stage-III CRCs and was prognostic overall for time to relapse (TTR), but not for DFS or OS (Sinicrope et al, 2013a).…”

Section: Msi As a Biomarker With Cetuximab Adjuvant Therapymentioning

confidence: 99%

“…2. Prognosis -Several studies have shown dMMR CRC has a better prognosis than MMR proficient (pMMR) CRC Guastadisegni et al, 2010;Klingbiel et al, 2015;Popat et al, 2005;Roth et al, 2010;Sinicrope et al, 2015). MSI tumours are less prone to lymph node (Mohan et al, 2016) and synchronous liver metastasis (Nordholm-Carstensen et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

118

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Section: Universal Screeningmentioning

confidence: 99%

Section: Msi As a Biomarker With Cetuximab Adjuvant Therapymentioning

confidence: 99%

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The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Ryan

Sheahan

Creavin

et al. 2017

Critical Reviews in Oncology/Hematology

100

118

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“…Deficient MMR can result from a germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2), that is, Lynch syndrome (LS). dMMR CRCs are notable for greater survivability, particularly in Stage II/III CRC 28, 30, 31. Retrospective studies have demonstrated improved survival in patients with MMR‐competent tumors after receiving 5‐FU‐based chemotherapy 32, 33.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

et al. 2018

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Interleukin (IL)‐37 and neutrophils are considered to be involved in human cancer, but their prognostic significance in colorectal cancer (CRC) has not been elucidated. The aim of this study was to evaluate the prognostic value of IL‐37 expression and neutrophil levels in CRC. We retrospectively analyzed IL‐37 expression, CD66b+ neutrophil levels, and mismatch repair (MMR) status in 337 paraffin‐embedded CRC specimens from the training cohort by immunohistochemistry. Their prognostic values were assessed using Kaplan‐Meier curves and multivariate Cox regression models. Moreover, several risk factors were used to form nomograms to evaluate survival, and the performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. Further validation was performed in an independent cohort of 245 cases. Low IL‐37 expression and high CD66b+ neutrophil levels were significantly associated with diminished disease‐free survival (DFS) and overall survival (OS), and patients with MMR‐deficient CRC had better clinical outcomes. Furthermore, multivariate Cox analysis identified IL‐37, CD66b+ neutrophils, and MMR status as independent prognostic factors for DFS and OS. Two nomograms integrating the three markers with four clinicopathological risk factors were developed and validated for predicting DFS and OS with good calibration and discrimination (C‐index: training cohort, 0.798 (95% confidence interval:0.764‐0.832) and 0.828 (0.796‐0.860), respectively; validation cohort, 0.739 (0.696‐0.783) and 0.761 (0.715‐0.808), respectively). Decision curve analysis demonstrated that the nomograms were clinically useful. Intratumoral IL‐37, CD66b+ neutrophils, and MMR status were independent prognostic factors for CRC patients. Nomograms incorporating these biomarkers and clinicopathological features could be conveniently used to facilitate the individualized prediction of DFS and OS.

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“…1,2 More importantly, MSI-H colorectal cancer is known as a better prognostic phenotype than MSI-low and microsatellite-stable (MSS) colorectal cancers. [3][4][5] Regarding the prognostic implications of MSI-H colorectal cancer, we previously reported an interesting result in which patients with CpG island methylator phenotypehigh (CIMP-H) displayed worse survival than those with CIMP-low/negative (CIMP-L/0) in MSI-H colorectal cancer. 6 Although the prognostic value of CIMP has been controversial in colorectal cancer, 1,[6][7][8][9] our previous study implied that MSI-H colorectal cancer is not a molecularly and prognostically homogeneous phenotype; therefore, it could be classified into prognostic subgroups depending on its underlying genetic or epigenetic status.…”

mentioning

confidence: 99%

Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size and patient prognosis in microsatellite-unstable colorectal cancer

Kim

Rhee

et al. 2014

Modern Pathology

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It has been recently suggested that the expression levels of mutant HSP110 could be a prognostic marker in colorectal cancer with a high level of microsatellite instability (MSI-H). The aim of our study was to validate the prognostic significance of HSP110 mutation using immunohistochemistry and DNA testing in MSI-H colorectal cancer. Wild-type HSP110 (HSP110wt)-specific immunohistochemistry was performed in 168 MSI-H colorectal cancer tissues, and their expression levels were evaluated using a four-tier scoring system (0/1 þ /2 þ /3 þ ). Of these tissues, 167 cases were analyzed for HSP110 T 17 deletion. Associations with clinicopathological, molecular and survival parameters were statistically analyzed. The low-level expression of HSP110wt (0/1 þ ) was observed in 40 MSI-H colorectal cancers (24%) and was significantly related to large HSP110 T 17 deletions (Z 4 bp, Po0.001). In survival analysis, patients with low HSP110wt expression (0/1 þ ) showed better diseasefree survival compared with those with high expression (2 þ /3 þ ; P ¼ 0.005). This significance in survival difference was maintained in patients with 5-fluorouracil-based chemotherapy-treated tumors (P ¼ 0.024) and in those with stage III/IV tumors (P ¼ 0.032). Multivariate analysis confirmed the role of HSP110wt expression as an independent prognostic factor (P ¼ 0.016, hazard ratio ¼ 4.32). In MSI-H colorectal cancer, a low expression of HSP110wt is associated with large HSP110 T 17 deletions and better clinical outcome. Immunohistochemistry of HSP110wt can be a simple and valuable tool for the prognostic and therapeutic stratification of patients with MSI-H colorectal cancer.

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Microsatellite instability as a marker of prognosis and response to therapy: A meta-analysis of colorectal cancer survival data

Cited by 346 publications

References 76 publications

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing

Prognostic significance of nomograms integrating IL‐37 expression, neutrophil level, and MMR status in patients with colorectal cancer

Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size and patient prognosis in microsatellite-unstable colorectal cancer

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