Differential expression patterns of hyaluronan receptors CD44 and RHAMM in transitional cell carcinomas of urinary bladder

Recurrence due to invasive growth is the major risk factor of transitional cell carcinoma (TCC) of urinary bladder. The interactions of hyaluronic acid (HA) and its receptors, CD44 and RHAMM, on cancer cells can promote invasion and metastasis but parallel study on these two genes in TCCs has not been available. The current work is aimed to address this issue by frozen tissue array-based immunocytochemical staining and Western blot hybridization. The results revealed that 19 out of 28 non-cancerous mucosa (68%) expressed CD44, in which 9 (33%) harbored variant exon 6 (v6). CD44 and v6 were both 5111 (46%) in papillary, non-invasive carcinomas (pTa) and 6/14 (43%) in the tumors remained in sub-epithelial layer (pT1), while 5/29 (17%) and 3/29 (10%) in pT2-4 invasive tumors. RHAMM expression was uncommon in non-cancerous mucosa (5/28) but became frequent in pTa (9/11), pT1 (12/14) and pT2-4 (24/29) tumors. RHAMM proteins were labeled intracellularly and showed more than one isoforms. Our data further confirm the promising prognostic value of CD44 for TCC patients and demonstrate, for the first time, the correlation between RHAMM expression and malignant transformation of urothelial cells.