Diminution of Primary Cilia in the Stromal Cells at the Tumor-stromal Interface Correlates With an Aggressive Tumor Biology in the Urothelial Carcinoma of the Urinary Bladder

Abstract

Background and Aims: Primary cilia (PC) are cellular organelles that regulate the cellular homeostasis. They are the seats of many oncogenic pathways and indirectly regulate the epithelial-mesenchymal transition (EMT) and extracellular matrix, both critical for the tumor microenvironment (TME). Though there are a few studies highlighting the alteration of PC in the tumor cells of various malignancies, none depict the PC in the stromal cells in the urothelial carcinoma of the urinary bladder (UC), the stromal cells being an essential component of TME. Therefore, we intend to evaluate the PC in the stromal cells at the tumor-stromal interface in UC. Methods: Immunohistochemistry for acetylated-α-tubulin (for PC), Ki67, E-cadherin, and SNAI1 was performed in 141 cases of UC and 5 normal controls, and primary cilium: nucleus (C:N) ratio was counted in the stromal cells at the tumor-stromal interface. The C:N ratio was correlated with various clinical and histopathological parameters. Results: The C:N ratio showed significant diminution from normal control (mean=0.75) to low-grade UC (mean=0.24) (P=0.001) to high-grade UC (mean value=0.17) (P=0.001). There was a significant diminution of the C:N ratio from the noninvasive to invasive UC (P=0.025). The C:N ratio did not show any correlation with EMT although negatively correlated with the Ki67 index (r=−0.32; P=0.001), and a higher ratio showed a trend with a higher recurrence-free survival (P=0.07). Conclusions: The diminution of the PC in the stromal cells at the tumor-stromal interface is an early event and correlates with an aggressive tumor biology of UC.