Background: Microsatellite instability (MSI) characterizes almost all Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases and 10–15% of sporadic colorectal cancer (CRC). The clinical outcome of these tumors and the role of MSI as prognostic factor is still debated, in particular for what concerns the relationship between chemotherapy and MSI. In this study, we examined whether MSI in CRC could carry further prognostic information. Methods: One thousand and two hundred and fifty CRC patients(pts) were addressed to MSI testing in the context of a population-based biomolecular screening or for clinical suspicion of HNPCC in 3 different institutions. All the tumors were tested with 3 mononucleotide markers (BAT25, BAT26 and BAT40) and by immunohistochemistry: tumors were defined MSI+ when instability was present in at least two loci. CRC specific survival was analyzed with Kaplan-Meier method in relation to MSI, sex, age at diagnosis, stage, grading, cancer subsite, histological type, diagnosis of HNPCC according to the presence of MMR genes mutation, chemotherapy. The independent effect of each variable was then tested through Cox regression multivariate analysis. Furthermore the effect of chemotherapy in stage II and III CRC pts were analyzed both in MSI and microsatellite stable (MSS) CRCs. Results: Two hundreds and forty three pts, of whom 42 HNPCC, were affected by MSI+ CRC. At the end of the observation period, 788 were alive. Log-Rank test revealed stage, age, MSI+ and grading significantly related to survival. Cox regression model confirmed the effect of these prognostic factors. Considering stage II and III colorectal cancers only, MSI confirms its independently significant prognostic role: in particular, prognosis of MSI CRC pts does not seem influenced by the use of chemotherapy, thus confirming what recently reported. Finally the observation, in univariate analysis, of a better prognosis in HNPCC patients than in the sporadic MSI counterpart, could be attributed to the different stage and age at diagnosis in the 2 groups. Conclusions: MSI in this sample including pts with hereditary CRC appears as independent prognostic factor in colorectal tumors and could be of help in optimizing the appropriate strategy of therapy and follow up.

Prognosis of colorectal cancer with microsatellite instability

GAFA', Roberta;LANZA, Giovanni;
2005

Abstract

Background: Microsatellite instability (MSI) characterizes almost all Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases and 10–15% of sporadic colorectal cancer (CRC). The clinical outcome of these tumors and the role of MSI as prognostic factor is still debated, in particular for what concerns the relationship between chemotherapy and MSI. In this study, we examined whether MSI in CRC could carry further prognostic information. Methods: One thousand and two hundred and fifty CRC patients(pts) were addressed to MSI testing in the context of a population-based biomolecular screening or for clinical suspicion of HNPCC in 3 different institutions. All the tumors were tested with 3 mononucleotide markers (BAT25, BAT26 and BAT40) and by immunohistochemistry: tumors were defined MSI+ when instability was present in at least two loci. CRC specific survival was analyzed with Kaplan-Meier method in relation to MSI, sex, age at diagnosis, stage, grading, cancer subsite, histological type, diagnosis of HNPCC according to the presence of MMR genes mutation, chemotherapy. The independent effect of each variable was then tested through Cox regression multivariate analysis. Furthermore the effect of chemotherapy in stage II and III CRC pts were analyzed both in MSI and microsatellite stable (MSS) CRCs. Results: Two hundreds and forty three pts, of whom 42 HNPCC, were affected by MSI+ CRC. At the end of the observation period, 788 were alive. Log-Rank test revealed stage, age, MSI+ and grading significantly related to survival. Cox regression model confirmed the effect of these prognostic factors. Considering stage II and III colorectal cancers only, MSI confirms its independently significant prognostic role: in particular, prognosis of MSI CRC pts does not seem influenced by the use of chemotherapy, thus confirming what recently reported. Finally the observation, in univariate analysis, of a better prognosis in HNPCC patients than in the sporadic MSI counterpart, could be attributed to the different stage and age at diagnosis in the 2 groups. Conclusions: MSI in this sample including pts with hereditary CRC appears as independent prognostic factor in colorectal tumors and could be of help in optimizing the appropriate strategy of therapy and follow up.
Benatti, P.; Marino, M.; Gafa', Roberta; Barana, D.; Pedroni, M.; Scarselli, A.; DI GREGORIO, C.; Roncucci, L.; Oliani, C.; Lanza, Giovanni; PONZ DE LEON, M.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11392/1204512
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