Differential expression of CD44 variant isoforms by cell lines and tissue specimens of transitional cell carcinomas.

Certain splice variants (CD44v) can promote the progressive and metastatic behavior of cancer. We tested whether different CD44v molecules were selectively expressed in transitional cell carcinomas based on the stage and grade. A panel of 13 TCC cell lines with different degrees of differentiation and biological behavior were tested with monoclonal antibodies to CD44s, CD44v5, v6, v7, v7-8 and v10 by two approaches: immunofluorescence/flow cytometry and immunocytochemistry. In addition, immunohistochemistry was performed on 55 TCC specimens. Immunofluorescence/flow cytometric analysis showed that surface expression of the variant isoforms CD44v5 and v6 were absent in 3/7 high-grade cell lines (MGH-U1, -U1R and CUB III). Immunohistochemistry showing moderate to strong expression of CD44s was found in 46 out of 55 bladder tumor tissues. Expression of CD44v5 was negatively related with tumor grade (p = 0.007), stage (p = 0.030) and recurrence (p = 0.019). Expression of CD44v10 correlated with tumor recurrence (p = 0.008), while that of CD44v6 did not show any correlation with tumor grade, stage or recurrence. Among the CD44 variant isoforms on 55 TCC tissue specimens examined, the expression of CD44v5 was inversely related to tumor grade, stage and recurrence, while the expression of CD44v10 was positively related to tumor recurrence. The CD44v10 may have potential to be developed as a specific immunotherapy target for selected urothelial TCCs.