Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis

Guetz, G. Des; Schischmanoff, Olivier; Nicolas, Patrick; Perret, Gérard-Yves; Morère, J. F.; Uzzan, Bernard

doi:10.1016/j.ejca.2009.04.018

Cited by 279 publications

(230 citation statements)

References 31 publications

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“…Ribic et al combining data from RCTs of patients receiving surgery only versus those who also received adjuvant 5-FU-based treatment showed that patients with MSI were potentially harmed by chemotherapy (Ribic et al, 2003). The finding that 5-FU-based chemotherapy did not seem to improve survival among MSI patients was supported by a large retrospective analysis of over a thousand patients (Benatti et al, 2005) and by a metaanalysis (Des Guetz et al, 2009) …”

Section: Predictive Significance Of Msi For 5-fu-based Chemotherapy (Seementioning

confidence: 99%

“…In MSI CRC, PD-L1 expression appears not to be on tumor cells, but rather on tumorinfiltrating lymphocytes and/or myeloid cells (Fusi et al, 2015; was not a pr edictive marker. (Benatti et al, 2005;Des Guetz et al, 2009;Hutchins et al, 2011;Ribic et al, 2003;Sargent et al, 2010;Webber et al, 2015). Llosa et al, 2015;Taube et al, 2014).…”

Section: Predictive Significance Of Msi For Immune Checkpoint Inhibitorsmentioning

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

118

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Section: Predictive Significance Of Msi For 5-fu-based Chemotherapy (Seementioning

confidence: 99%

Section: Predictive Significance Of Msi For Immune Checkpoint Inhibitorsmentioning

confidence: 99%

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

118

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“…3,10 In contrast to MSS colorectal cancer, a trend toward chemoresistance, especially toward 5-fluorouracil (5-FU)-based chemotherapy, has been observed in MSI-H colorectal cancer. 4,[11][12][13][14][15] In fact, there is a lack of evidence regarding molecular factors that might predict responses to chemotherapy or sophisticatedly stratify prognoses in MSI-H colorectal cancer. 16 Although the BRAF V600E mutation has been thought to be related to a poor prognosis in colorectal cancer, 1,17 its prognostic effect was significant only in MSS colorectal cancer, not in MSI-H colorectal cancer.…”

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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“…On the other hand, the influence of MMR gene status on treatment outcome during chemotherapy [10][11][12][13] and the potential connection with indirect signs of immune reaction are still lacking in the published literature.…”

Section: Introductionmentioning

confidence: 99%

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

et al. 2016

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Introduction The microsatellite-instable gastric cancer subtype, because of its supposed high antigenic potential, is a promising candidate for immunotherapy. We analyzed if the presence of a defective mismatch repair (MMR) system is associated with other markers of immune response and their relationship with outcome in advanced gastric cancer patients. Methods We analyzed the relationship between clinical outcome and MMR status, the presence of tumor-infiltrating lymphocytes (TIL), lymphocytosis, and neutrophil-tolymphocyte ratio (NLR) in metastatic gastric cancer patients treated with a chemotherapy doublet in the firstline setting. Other stratification factors were sex, age, Eastern Cooperative Oncology Group performance status, adjuvant/neoadjuvant chemotherapy, metastatic sites, and histotype. Results One hundred three patients were eligible for analysis. Defective MMR was found in 15 patients (14 %), TILs were found in 18 patients (17 %), lymphocytosis was found in 24 patients (23 %), and high NLR was found in 75 patients (72 %). Significant correlations were found between defective MMR and TIL positivity (p = 0.0004), between defective MMR and lymphocytosis (p = 0.0062), between defective MMR and low NLR (p = 0.000069), and between TIL positivity and lymphocytosis (p = 0.000147). All factors had a statistically significant impact on overall survival, although on multivariate analysis only defective MMR (p = 0.0001) and TIL positivity (p = 0.0192) maintained their independent prognostic role. Similar results were observed for progression-free survival, with defective MMR (p = 0.0001) and TIL positivity (p = 0.0195) maintaining their prognostic role on multivariate analysis. Conclusions Our analysis confirms the favorable prognosis of metastatic gastric cancer patients with a defective MMR system and suggests that expression of TILs might also be linked to better outcome. Because of the correlation between defective MMR status and measures of immune system activity, this group of patients would be the best candidates for novel immunotherapy-based therapies.

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Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis

Cited by 279 publications

References 31 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

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

Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy

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