Background. Colorectal cancer (CRC) is characterized by a multistep progression of genetic errors. Two different pathways are identified, that of chromosomal instability (CIN) and the microsatellite instability (MSI) pathway. Widespread microsatellite instability (MSI high, MSI-H phenotype) is present in 10-20% of sporadic colorectal cancers and characterizes patients with the inherited Lynch syndrome (Hereditary non polyposis colorectal cancer, HNPCC). MSI-H tumors have distinctive pathologic features, and are believed to behave less aggressively when compared with tumors that lack microsatellite instability (microsatellite stable, MSS) or that show instability at a few loci (microsatellite low, MSI-L phenotype). Methods. We studied 340 consecutive CRCs for MSI using multiplexed polymerase chain reaction (PCR) for 12 microsatellite markers followed by capillary electrophoresis with a DNA sequencer. DNA was extracted from routinely processed formalin-fixed tissue. All surgical specimens underwent routine histopathological analysis for grading and staging. Tumors were considered MSI-H when 4 or more of the 12 loci were mutated , MSI-L when 1-3 loci were mutated and MSS when no mutations were identified. Results. 40 CRCs were MSI-H (11,5%), 45 CRCs were MSI-L (13,5%) and 255 CRCs were MSS (75%). Correlation with clinicopathologic features confirms previous findings that show how MSI-H CRCs are more common in the right colon, display poorly differentiated histologic features and show prominent lymphocytic infiltration when compared with MSI-L and MSS tumors. Survival analysis after a median follow-up of 45 months shows that MSI-H tumors have a better prognosis in patients with stage 1 and 2 disease, but the prognosis is considerably worse for stage 3 and 4 disease (p<0.01) that received standard chemotherapy treatment. Conclusions. MSI-H CRCs show distinctive clinical and pathological features. In our series patients survival depended on tumor stage at presentation. The results of the study argue for MSI testing on routinely processed CRCs.

Microsatellite instabilityDNA testing in routinely processed colorectal carcinomas: correlation with clinicopathologic and survival data in 340 consecutive cases

TOSI, ANNA LISA;MORANDI, LUCA;DE BIASE, DARIO;PESSION, ANNALISA;TURCHETTI, DANIELA;TALLINI, GIOVANNI
2010

Abstract

Background. Colorectal cancer (CRC) is characterized by a multistep progression of genetic errors. Two different pathways are identified, that of chromosomal instability (CIN) and the microsatellite instability (MSI) pathway. Widespread microsatellite instability (MSI high, MSI-H phenotype) is present in 10-20% of sporadic colorectal cancers and characterizes patients with the inherited Lynch syndrome (Hereditary non polyposis colorectal cancer, HNPCC). MSI-H tumors have distinctive pathologic features, and are believed to behave less aggressively when compared with tumors that lack microsatellite instability (microsatellite stable, MSS) or that show instability at a few loci (microsatellite low, MSI-L phenotype). Methods. We studied 340 consecutive CRCs for MSI using multiplexed polymerase chain reaction (PCR) for 12 microsatellite markers followed by capillary electrophoresis with a DNA sequencer. DNA was extracted from routinely processed formalin-fixed tissue. All surgical specimens underwent routine histopathological analysis for grading and staging. Tumors were considered MSI-H when 4 or more of the 12 loci were mutated , MSI-L when 1-3 loci were mutated and MSS when no mutations were identified. Results. 40 CRCs were MSI-H (11,5%), 45 CRCs were MSI-L (13,5%) and 255 CRCs were MSS (75%). Correlation with clinicopathologic features confirms previous findings that show how MSI-H CRCs are more common in the right colon, display poorly differentiated histologic features and show prominent lymphocytic infiltration when compared with MSI-L and MSS tumors. Survival analysis after a median follow-up of 45 months shows that MSI-H tumors have a better prognosis in patients with stage 1 and 2 disease, but the prognosis is considerably worse for stage 3 and 4 disease (p<0.01) that received standard chemotherapy treatment. Conclusions. MSI-H CRCs show distinctive clinical and pathological features. In our series patients survival depended on tumor stage at presentation. The results of the study argue for MSI testing on routinely processed CRCs.
Pathologica
370
370
A.L. Tosi; L. Morandi; D. De Biase; A. Pession; A. Maestri; D. Turchetti; P. Baccarini; M. Brulatti; G. Tallini
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/104280
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