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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 < 0.0001). In vitro levels of IFN-γ ( P = 0.004) and IL-18 ( P < 0.0001) mirrored these differences in lymphocyte activity. Conclusions Stratification of colorectal cancer by MSI and ploidy status may have prognostic value in patients undergoing curative surgery. MSI-H cancers display enhanced immunogenic properties but the immune response to MACS cancers appears to be absent and this may contribute to their poor prognosis. [ABSTRACT FROM AUTHOR]

Objective We have carried out a retrospective analysis of all cases of colorectal cancer at the Royal London Hospital between April 1998 and March 2002 and determined the differences in presentation and outcome between Bangladeshi and Non-Bangladeshi patients. DNA microarrays were used to explain any potential genetic differences between these two groups that may explain the different phenotypes. Materials and methods We examined the colorectal database at our institution. Microarray profiles, using Affymetrix HU133A Genechips™ (Santa Clara, CA USA) were obtained from 10 Bangladeshi patients and an age-, sex- and stage-matched group of 10 Non-Bangladeshi patients. Results Three hundred and sixty-three patients have been treated for colorectal cancer at the Royal London Hospital. Eighteen (5%) patients were of Bangladeshi origin. The prevalence was 27/100 000 compared to 342/100 000 of the Non-Bangladeshi population. Eleven (61%) of 18 Bangladeshi patients were under the age of 40 and 4 (22%) patients presented with locally advanced or metastatic disease. In comparison 39/345 (11%) of non-Bangladeshi patients presented with advanced disease. None of the Bangladeshi patients gave a positive family history. Microarray profiling between these two groups demonstrated 1203 differentially expressed genes ( P < 0.05). Conclusion Colorectal cancer is uncommon in the Bangladeshi patients compared to the non-Bangladeshi population. This cancer presents in younger patients and at a more advanced stage. There is no positive family history within this ethnic community and therefore the cancers are sporadic. However, microarray profiling is able to delineate different gene expression between these two groups. Therefore, there should be a low threshold for investigating young Bangladeshi patients with symptoms of colorectal neoplasia and any future national screening programme should allow for ethnic variation. [ABSTRACT FROM AUTHOR]