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.

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