Intratumoral heterogeneity of CD44v6 in rectal cancer.

PURPOSE: CD44v6 plays a controversial role in tumor progression and patient outcome in colorectal cancer by plenty of conflicting reports. The purpose of this study was to profile the intratumoral heterogeneity of CD44v6 in rectal cancer and investigate its role in lymph node metastasis. METHODS: Sixty patients were included in this study. Immunohistochemistry for CD44v6 was performed in normal mucosa, primary tumor, and lymph node metastasis with whole tissue sections. The staining intensity in tumor center and invasive front was separately measured. Sampling bias was evaluated by quantitative real-time PCR with 15 pairs of frozen tissues from different sites of the primary tumor. RESULTS: CD44v6 expression increased from normal mucosa to primary tumor to lymph node metastasis. Multiple intratumoral staining patterns was observed in primary tumor, and CD44v6 expression in invasive front was significantly higher than that in tumor center. In addition, mRNA expression levels differed across different geographical regions of the tumor. No association between CD44v6 expression and lymph node metastasis was revealed. CONCLUSIONS: Substantial intratumoral heterogeneity of CD44v6 exists in rectal cancer that impacts the outcome of individual studies. CD44v6 expression should be assessed in a more precise way with a specified staining pattern and in a designated location.