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The aim of this study was to determine the predictive and prognostic value of epidermal growth factor receptor (EGFR) expression in rectal cancers treated with preoperative high-dose rate brachytherapy and in mismatch-repair (MMR)-proficient colorectal cancers (CRCs), respectively. We validate the use of receiver operating characteristic (ROC) curve analysis to select cutoff scores for EGFR overexpression for the end points studied. Immunohistochemistry (IHC) for EGFR was performed on 82 rectal tumour biopsies and 1197 MMR-proficient CRCs using a tissue microarray. Immunoreactivity was scored as the percentage of positive tumour cells by three pathologists and the inter-observer reliability was assessed. ROC curve-derived cutoffs were used to analyse the association of EGFR overexpression, tumour response and several clinicopathological features including survival. The scoring method was found to be reproducible in rectal cancer biopsies and CRCs. The selected cutoff scores from ROC curve analysis for each clinicopathological feature were highly consistent among pathologists. EGFR overexpression was associated with response to radiotherapy (P-value o0.001) and with worse survival time (P-value o0.001). In multivariate analysis, EGFR overexpression was independently associated with adverse prognosis (P-value o0.001). Epidermal growth factor receptor is a predictive marker of response to preoperative radiotherapy and an independent adverse prognostic factor CRC.

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SummaryWe have reported previously that naive T cells from relapsing-remitting multiple sclerosis (RRMS) patients have T cell receptor (TCR) repertoire shifts, but the basis of these TCR repertoire shifts was uncertain. Here, we questioned whether RRMS patients have altered naive CD4 and CD8 T cell homeostasis by studying homeostatic proliferation and thymic production in RRMS patients and healthy controls. We measured thymic production by quantifying signal joint T cell receptor excision circles (sjTRECs). Both naive T subsets from controls showed an age-associated decrease in sjTRECs, i.e. evidence of progressive thymic involution, but we detected no age-associated decrease in sjTRECs in RRMS patients. Instead, naive CD8 T cells from patients had lower sjTRECs ( P = = = = 0·012) and higher Ki-67 proliferation levels ( P = = = = 0·04) than controls. Naive CD4 T cell sjTRECs did not differ between patients and controls. However, in RRMS these sjTRECs correlated strongly with CD31, a marker expressed by newly generated CD4 T cells but not by naive CD4 T cells that have undergone homeostatic proliferation. HLA-DR2 positivity correlated negatively with naive CD4 T cell CD31 expression in RRMS ( P = = = = 0·002). We conclude in RRMS that naive T subsets have homeostatic abnormalities due probably to peripheral (non-thymic) mechanisms. These abnormalities could have relevance for MS pathogenesis, as naive T cell changes may precede MS onset.

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