1. ¹Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, 880, Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan
2. ²Department of Gastroenterology, Dokkyo University School of Medicine, 880, Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan

Correspondence: Dr H Fukui, E-mail: h-fukui@dokkyomed.ac.jp

Received 12 December 2007; Revised 27 March 2008; Accepted 27 March 2008; Published online 29 April 2008.

Abstract

Although stromal cell-derived factor (SDF)-1 and its receptor CXCR4 are experimentally suggested to be involved in tumorigenicity, the clinicopathological significance of their expression in human disease is not fully understood. We examined SDF-1 and CXCR4 expression in colorectal cancers (CRCs) and their related lymph nodes (LNs), and investigated its relationship to clinicopathological features. Specimens of 60 primary CRCs and 27 related LNs were examined immunohistochemically for not only positivity but also immunostaining patterns for SDF-1 and CXCR4. The relationships between clinicopathological features and SDF-1 or CXCR4 expression were then analysed. Stromal cell-derived factor-1 and CXCR4 expression were significantly associated with LN metastasis, tumour stage, and survival of CRC patients. Twenty-nine of 47 CXCR4-positive CRCs (61.7%) showed clear CXCR4 immunoreactivity in the nucleus and a weak signal in the cytoplasm (nuclear type), whereas others showed no nuclear immunoreactivity but a diffuse signal in the cytoplasm and at the plasma membrane (cytomembrane type). Colorectal cancer patients with nuclear CXCR4 expression showed significantly more frequent LN metastasis than did those with cytomembrane expression. Colorectal cancer patients with nuclear CXCR4 expression in the primary lesion frequently had cytomembrane CXCR4-positive tumours in their LNs. In conclusion, expression of SDF-1 and nuclear CXCR4 predicts LN metastasis in CRCs.