Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression

Bladder cancer is one of the most common malignant diseases. Since a high-rate of recurrence is a serious problem for early stage urothelial carcinomas, new strategies for the management of recurrent urothelial carcinomas have been explored. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein and is expressed in various cancer tissues, mainly squamous cell carcinomas. CD109 negatively controls transforming growth factor (TGF)-β/Smad signaling in vitro. In this study, we analyzed the clinical significance of CD109 expression in bladder cancer using immunohistochemistry. Of 156 urothelial carcinoma tissues, 69.9% were positive for CD109, whereas CD109 was not expressed in seven normal bladder epithelia. CD109 expression was significantly higher in non-muscle-invasive (pTa+pT1) or low-grade (G1+G2) tumors than in muscle-invasive (pT2-4) or high-grade (G3) tumors, and was associated with cancer-specific survival. Simultaneous immunostaining of CD109 and phosphorylated Smad2 showed an inverse immunoreactivity relationship between the two, suggesting that CD109 inhibits TGF-β/Smad signaling in tumor tissues. Interestingly, CD109 was found to be highly expressed in the basal layer of non-invasive urothelial carcinomas, and the expression pattern was similar to that of CD44, a marker of cancer stem cells. These findings suggest that CD109 is involved in bladder tumorigenesis and is a potential target for cancer immunotherapy.