Reduced expression of syndecan-1 correlates with histologic dedifferentiation, lymph node metastasis, and poor prognosis in intrahepatic cholangiocarcinoma.

Syndecan-1, a cell-surface transmembrane heparan sulfate proteoglycan, has been reported to correlate with the biologic behavior of malignant tumors in various organs. We examined the correlation between the expression of syndecan-1 at the protein and mRNA levels and clinicopathologic features of 37 intrahepatic cholangiocarcinomas (ICCs). Noncancerous bile duct epithelial cells showed basolateral membranous expression of syndecan-1, whereas ICC cells showed membranous and also diffuse cytoplasmic expression. In situ hybridization demonstrated a distribution of syndecan-1 mRNA similar to that of the protein in carcinoma tissue, suggesting that syndecan-1 expression in ICC is regulated at the transcriptional level. Reduction of syndecan-1 expression in carcinoma was associated with poor histological differentiation (P <0.01): syndecan-1 expression was intense and extensive in well-differentiated (10 cases) and largely negative or weakly positive in poorly differentiated (13 cases) adenocarcinoma, and its expression in moderately differentiated tumors (14 cases) was intermediate. Patients with ICCs demonstrating negative or weak expression of syndecan-1 frequently had lymph node metastases and had a rather poor prognosis after surgical resection compared with those whose tumors demonstrated moderate or strong expression (P <0.05). However, syndecan-1 expression was not correlated with tumor size, stromal desmoplasia, gross classification, vascular invasion, or perineural invasion. We conclude that expression of syndecan-1 could correlate with some aspects of the biologic behaviors of ICCs and may be a useful prognostic marker.