Abstract
Bladder urothelial carcinoma subtypes identified with gene expression profiling need to be bridged over to
routine clinical practice. A simple immunohistochemical panel of markers was applied to 192 specimens, and
the 4 major subgroups were identified in 92.2% without overlap. The identified characteristics of urothelial
carcinoma detected in our population can be used for individualized treatment planning.
Background: Although gene expression profiling provided a comprehensive molecular characterization of different
subtypes of bladder urothelial carcinoma (UC), which are distinct in their biological features and prognosis, such a
system is not yet applicable for routine clinical practice. This study aimed to examine the expression of these molecular classes of UC using simple panel of immunohistochemical markers. Materials and Methods: Tissue sections
from 192 specimens of UC were stained with FGFR3, CK5, CCNB1, HER-2, and P53. The molecular classes identified
were correlated with clinicopathologic characteristics and patient survival. Results: The most frequent class in our
cohort was urobasal B (UroB) (44.1%), followed by squamous cell carcinoma-like (SCCL) (22%), genomically unstable
(GU) (20.3%), and urobasal A (UroA) (13.6%). Patients with SCCL were significantly younger (P < .0001). Both the
SCCL and GU types were of significantly higher histopathologic grade (P < .0001). UroA tumors were mainly of the T1
stage (75%), whereas 61.5% of the SCCL and 58.3% of the GU types were of stage T2 (P < .001). Prognosis was
significantly different among groups. The SCCL class showed the lowest overall survival (38.5%; P ¼ .030) and
metastasis-free survival (69.2%; P ¼ .017). The best prognosis was for UroA, with an overall survival of 75% and no
metastatic events. Conclusion: The distribution of UC subtypes in our study was uniquely different from other studies.
This simple immunohistochemical panel could be suggested as a clinically applicable tool that has the potential to be
used routinely in guiding individualized treatment of UC.