Systematic assessment of the prognostic impact of membranous CD44v6 protein expression in colorectal cancer

Aims: To assess systematically the membranous expression of CD44v6 in colorectal cancer by immunohistochemistry to determine its prognostic impact, the differential expression between primary and metastatic tumours and expression differences between the tumour centre and invasive front. Methods and results: Immunohistochemistry was performed for CD44v6 on two tissue microarrays. The first included 1279 colorectal tumours with full clinicopathological data. The second consisted of 50 matched primary and metastatic tumours sampled from the tumour centre and the invasive margin. A scoring system was tested by multiple observers. Receiver-operating characteristic curve analysis was used for cut-off point determination. Loss of membranous CD44v6 was associated with pT stage (P = 0.016; sensitivity 85.8%, specificity 20.1%), lymph node metastasis (P = 0.015; sensitivity 52.8%, specificity 55%), an infiltrating tumour margin (P > 0.001; sensitivity 71.4%, specificity 40%) and adverse prognosis (P = 0.011; hazard ratio 0.79, 95% confidence interval 0.7, 0.9), but was not an independent prognostic factor on multivariable analysis. Loss of expression occurred at the invasive front in both primary and metastatic lesions (P > 0.001). Conclusions: This study outlines an approach to help standardize the immunohistochemical evaluation of CD44v6 and similar markers in colorectal cancer and highlights a significant role for loss of membranous CD44v6 expression in colorectal cancer progression and prognosis.