Loss of CD44 variant 6 expression differentiates small cell carcinoma of urinary bladder from urothelial (transitional cell) carcinoma

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Abstract
Small cell carcinoma of the urinary bladder has a more aggressive biological potential than urothelial carcinoma, but its morphology may overlap with poorly differentiated urothelial carcinoma. The CD44 family of glycoproteins mediates cell–cell and cell–matrix adhesion. Aberrant regulation of expression of CD44, and particularly its v6 variant exon, has been correlated with aggressive or metastatic phenotype of some cancers. We measured the degree of protein expression of CD44v6 in small cell and urothelial bladder carcinoma. Immunohistochemical staining was performed with monoclonal antibodies against CD44v6. Immunoreactivity was absent in 25 of 27 cases of small cell carcinoma, with two showing only weak staining of fewer than 10% of cells. In contrast, all 12 cases of moderately or poorly differentiated urothelial carcinoma displayed moderately intense reactivity in 50% to 100% of cells. CD44v6 immunostaining discriminates cases of poorly differentiated urothelial carcinoma from small cell carcinoma. It also highlights the presence of mixed small cell urothelial differentiation when present.