Carcinoembryonic antigen out-performed other markers dramatically in all three measures, showing the most frequent tumour expression, and the most frequent and best tumour overexpression (Figures 2 and ?and3).3). made up of main colorectal carcinoma and matched normal colorectal mucosa, collected prospectively for the MRC CLASICC trial (Guillou antibody (clone BN3.2; Leica Biosystems, Newcastle, UK) has been validated across a wide range of tissues, including colorectal tissue (Smith showed moderate cytoplasmic staining only, and was scored solely for this. Epithelial Aspartame growth factor receptor showed membranous, and C more rarely C cytoplasmic and nuclear staining. However, following established literature (Scartozzi and EGFR in a cohort of 280 colorectal carcinomas and matched normal tissues. Clinical and pathological features of this cohort are shown in Table 1. Representative images of staining for each antigen in both normal and tumour tissues are shown in Physique 1. All four markers showed epithelial cell specific staining that Aspartame was diffuse with some luminal accentuation. No staining for any marker was noted in blood cells within the sections, suggesting that expression in this compartment is usually negligible. The intra-class correlation coefficient was 0.89, demonstrating good agreement between scorers. Both the proportion of epithelial cells staining positively and the intensity of staining varied widely throughout the cohort in normal and tumour tissues (Physique 2). Strongly positive staining in normal tissues was relatively uncommon for all those antigens, especially for FR(unfavorable in over 99% at the concentrations used). In the tumours, by contrast, strongly positive staining was prevalent for CEA and TAG-72, and was more common for FRthan in normal tissue although tumours were also mostly unfavorable (61%). Epithelial growth factor receptor staining in tumours showed a similar range of scores to those in normal tissues. Carcinoembryonic antigen, TAG-72 and FRin normal colorectal tissue (left) and in colorectal tumours (right). Expression levels were decided in 280 matched normal and tumour tissues by immunohistochemistry using semi-quantitative scores of 0C15. The scores for each marker are arranged independently in ascending order to demonstrate the distributions Aspartame across the cohort. Table 2 CEA, TAG-72 and FRare significantly more highly expressed in colorectal tumour tissue than matched normal tissue and EGFR, respectively. Although this percentage is usually relatively low Aspartame for FRit should be noted that expression was higher in tumours as compared with matched normal tissue in almost all cases where positive staining was detected in either tissue. However, in the case of EGFR, expression was higher in normal tissue (34% of cases) more frequently than in tumours (33% of cases), indicating little or no bias for tumour-specific expression. We have estimated the magnitude of the differences in expression between matched tumour and normal tissues as the tumour expression score minus the normal expression score (Physique 3). Carcinoembryonic antigen exhibited the greatest difference in expression, with tumours scoring on average 10.8 (95% CI 10.31C11.21) points higher than normal tissues. This difference was more than twice that of the next best marker, TAG-72, which showed tumour expression 5.1 (95% CI 4.35C5.77) points higher than normal tissue, while FRand EGFR showed only very small increases in expression within the tumours. Open in a separate window Physique 3 Carcinoembryonic antigen shows the most consistent overexpression in tumour tissues and the greatest differential expression between matched normal and tumour tissues. Left: Expression scores for normal tissues were subtracted from those for matched tumour tissues to quantify the degree of tumour overexpression for each case. Overexpression scores for each marker Rabbit Polyclonal to OR8I2 are arranged in ascending order to demonstrate the distributions across the cohort (left). Minus scores reflect cases where tumour expression was lower than expression in the matched normal tissue. Mean overexpression scores (central marker) with 95% confidence intervals (error bars) are also shown (right). Expression of markers in lymph nodes If.