TY - JOUR
T1 - Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression
AU - Hagikura, Minako
AU - Murakumo, Yoshiki
AU - Hasegawa, Masaki
AU - Jijiwa, Mayumi
AU - Hagiwara, Sumitaka
AU - Mii, Shinji
AU - Hagikura, Shoichi
AU - Matsukawa, Yoshihisa
AU - Yoshino, Yasushi
AU - Hattori, Ryohei
AU - Wakai, Kenji
AU - Nakamura, Shigeo
AU - Gotoh, Momokazu
AU - Takahashi, Masahide
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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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U2 - 10.1111/j.1440-1827.2010.02592.x
DO - 10.1111/j.1440-1827.2010.02592.x
M3 - Article
C2 - 20946523
AN - SCOPUS:77958484263
SN - 1320-5463
VL - 60
SP - 735
EP - 743
JO - Pathology International
JF - Pathology International
IS - 11
ER -
