Clinical Outcome Of Patients With Msih Colorectal Tumors

Considering the different molecular and histological features of tumors with microsatellite instability and chromosomal instability (see introduction) one could expect that cancers emerging from MSI-H and CIN pathways would also differ in clinically relevant characteristics. Several studies investigating MSI-status and prognosis show that survival of patients with the MSI-H

phenotype is longer than that of patients with MSS cancers. However, some conflicting reports let the National Cancer Institute workshop conclude that MSI-H has not been demonstrated to be an independent predictor of prognosis.[6] These results may be due to both inconsistent definitions of MSI before 1998 and retrospective investigation of small patient cohorts. In a relatively large population-based study, the clinical outcome of MSI-H and MSS patients was assessed and associated with classic clinical prognostic factors. Highly frequent MSI was independently associated with prolonged survival in patients without adjuvant chemother-apy.[17] In another study, MSI-H correlated with lower tumor stage indicating that either MSI-H contributes to improved survival independently of other prognostic factors or MSI-H is independently predictive of lower pathological stage, thus contributing to the improved survival through tumor downstaging.[18] The reason why MSI-H improves clinical outcome is not clear yet. One can assume that the MSI-H typical mutation spectrum, i.e., small genomewide mutations, leads to mutation within coding repeats in genes of cell surface proteins thereby provoking an intense lymphocytic infiltrate and attack of the tumor.[19]

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