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• W4361944895 abstract "<div>Abstract<p><b>Purpose:</b> Patients with colorectal cancers (CRC) and high microsatellite instability (MSI) have a better outcome than their chromosome-unstable counterpart. Given the heterogeneity of microsatellite-unstable CRCs, we wanted to see whether any MSI-associated molecular features are specifically associated with prognosis.</p><p><b>Experimental Design:</b> One hundred and nine MSI-high CRCs were typed for primary mismatch repair (MMR) defect and for secondary loss of MMR proteins. Frameshifts at seven target genes, mutations in the RAS pathway, and methylation at <i>MLH1</i>/<i>CDKN2A</i> promoters were also searched. The interplay of molecular findings with clinicopathologic features and patient survival was analyzed.</p><p><b>Results:</b> Of 84 MLH1-deficient CRCs, 31 (36.9%) had MSH3 and 11 (13.1%) had MSH6 loss (<i>P</i> < 0.001), biallelic frameshift mutations at mononucleotide repeats accounting for most (78%) MSH3 losses. As compared with MSH3-retaining cancers, MLH1-deficient tumors with MSH3 loss showed a higher number of mutated target genes (3.94 ± 1.56 vs. 2.79 ± 1.75; <i>P</i> = 0.001), absence of nodal involvement at pathology [N0; OR, 0.11; 95% confidence interval (CI), 0.04–0.43, <i>P</i> < 0.001], and better disease-free survival (<i>P</i> = 0.06). No prognostic value was observed for KRAS status and for <i>MLH1</i>/<i>CDKN2A</i> promoter methylation. The association between MSH3 loss and N0 was confirmed in an independent cohort of 71 MLH1-deficient CRCs (OR, 0.23; 95% CI, 0.06–0.83, <i>P</i> = 0.02).</p><p><b>Conclusions:</b> MLH1-deficient CRCs not expressing MSH3 have a more severe MSI, a lower rate of nodal involvement, and a better postsurgical outcome. <i>Clin Cancer Res; 18(11); 3142–53. ©2012 AACR</i>.</p></div>" @default.
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• W4361944895 date "2023-03-31" @default.
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• W4361944895 title "Data from MSH3 Protein Expression and Nodal Status in MLH1-Deficient Colorectal Cancers" @default.
• W4361944895 doi "https://doi.org/10.1158/1078-0432.c.6521039" @default.
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