Immunohistochemical, molecular, and clinicopathological analyses of urothelial carcinoma, micropapillary variant

The prognosis of urothelial carcinoma, micropapillary variant (MPV), of the bladder has been shown to be worse than that of the conventional urothelial carcinoma (UC). However, it remains to be clarified why the MPV is more aggressive. We therefore here focused on the correlation between clinical features and histological, immunohistochemical and molecular findings for eight MPV and 35 UC, evaluating expression of MUC1, Ki-67, p53, CD147, CD34, D2-40, and extracellular matrix proteins. The Ki-67 labeling index was significantly higher in UC than in MPV but densities of venous and lymphatic tumor emboli were significantly higher in the MPV cases and lymph node metastasis was more frequent, with a poorer prognosis. Tenascin-C and fibronectin also showed significantly greater expression in MPV than in UC at the epithelial-mesenchymal interfaces. Direct sequencing showed point mutations of KRAS exon 1 in three MPV with significantly more frequency compared to UC. Occupation rate of the MPV area in the tumor showed significant inverse correlation with overall survival. Thus our histopathological findings provide clues to explaining why prognosis is poorer in the MPV than UC.