Microsatellite and chromosomal stable colorectal cancers demonstrate poor immunogenicity and early disease recurrence

Objective  Colorectal cancers may demonstrate chromosomal instability (CSI) or microsatellite instability (MSI‐H). A third group of microsatellite and chromosome stable (MACS) colorectal cancer has been described more recently. Patients with MSI‐H colorectal cancers demonstrate improved outcome and...

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Bibliographic Details
Published in:Colorectal disease 2009-07, Vol.11 (6), p.601-608
Main Authors: Banerjea, A., Hands, R. E., Powar, M. P., Bustin, S. A., Dorudi, S.
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aneuploidy
Cell Proliferation
Chromosomal Instability - genetics
Chromosomal Instability - immunology
Colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - immunology
Diploidy
Disease-Free Survival
Female
Follow-Up Studies
Humans
Immunogenetic Phenomena
immunogenicity
instability
Kaplan-Meier Estimate
Lymphocytes - immunology
Male
Microsatellite Instability
Middle Aged
Neoplasm Recurrence, Local - genetics
Neoplasm Recurrence, Local - immunology
Phenotype
recurrence
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Summary:Objective  Colorectal cancers may demonstrate chromosomal instability (CSI) or microsatellite instability (MSI‐H). A third group of microsatellite and chromosome stable (MACS) colorectal cancer has been described more recently. Patients with MSI‐H colorectal cancers demonstrate improved outcome and a pronounced inflammatory infiltrate. Enhanced host immune response and increased immunogenicity might explain these observations. This study aims to further characterize colorectal cancer immunogenicity. Method  Microsatellite stability status was determined in resected tumour samples. Microsatellite stable (MSS) tumour samples were stratified by DNA ploidy status, as determined by flow cytometry into aneuploid MSS (CSI) and diploid MSS (MACS) cancers. Lymphocyte proliferation, quantified by bromodeoxyuridine incorporation assays assessed tumour protein immunogenicity and ELISA assays quantified inflammatory cytokine release. Kaplan–Meier survival curves and multivariate analyses were used to determine prognostic value. Results  Patients with MSI‐H colorectal cancer had improved outcome but those with MACS cancers undergoing curative surgery had significantly poorer disease‐free survival (P = 0.002). The MACS phenotype was an independent predictor of poor outcome (HR = 2.44, 1.33–4.47, P = 0.004). Lymphocyte proliferation assays confirmed enhanced immunogenicity of MSI‐H proteins and reduced immunogenicity of MACS proteins (P 
ISSN:1462-8910
1463-1318
DOI:10.1111/j.1463-1318.2008.01639.x