Difference in expression of CD44 splice variants between proximal and distal adenocarcinoma of the large bowel

To help determine whether adenocarcinomas of the proximal and distal large bowel reflect distinct entities, the expression of two splice variants of the metastasis-associated cell adhesion molecule CD44, carrying exons v5 and v6 respectively, was investigated retrospectively in fresh frozen samples of 23 proximal and 41 distal carcinomas by immunohistochemical staining with specific anti-CD44v5 monoclonal antibody VFF8 and anti-CD44v6 monoclonal antibodies VFF4 and VFF7. Tumours were staged as: Dukes A, 0; Dukes B, 27; Dukes C, 31; and Dukes 'D', six. Compared with distal tumours, proximal lesions expressed significantly more CD44v5 (96 versus 87 per cent, P = 0.02) and CD44v6 (83 versus 61 per cent, P = 0.01). CD44v5 and CD44v6 are considered markers for tumour progression and aggressive behaviour. Their high expression in proximal carcinomas seems to contrast with the general belief that these tumours show less aggressive behaviour than left-sided lesions. Further study of the biological significance of the expression of CD44 splice variants is therefore needed.