Diminution of the Primary Cilia From the Intrahepatic Cholangiocytes in a Pediatric Choledochal Cyst

Abstract

Choledochal cyst (CC) is a cystic disease predominantly involving the extrahepatic biliary tree. Biliary atresia (BA), another disorder of the extrahepatic biliary tree, is sometimes considered to be in the same spectrum as pediatric CC. Recently, the absence and/or the structural abnormality of the primary cilia in the intrahepatic cholangiocytes have been implicated in the pathogenesis of BA. We aimed to evaluate the expression of primary ciliary proteins in the intrahepatic cholangiocytes in cases of pediatric CC and compare it with normal control and BA. We performed immunohistochemistry for primary ciliary proteins (acetylated-α-tubulin and double-cortin domain containing 2) on the liver biopsies of control liver (n = 5), pediatric CC (n = 13), and BA (n = 14). We also compared the expression with various clinical, biochemical, histopathologic (portal fibroinflammation and ductal plate malformation), and immunohistochemical (proliferative index) data. There was significant loss of primary cilia from the intrahepatic cholangiocytes in cases of CC and BA as compared with the normal control by both immunostains (CC: P = 0.003 and 0.001, respectively; BA: P = 0.001 and 0.001, respectively). There was no significant difference between the CC and BA in terms of ciliary protein loss. The loss of the ciliary proteins occurred irrespective of the proliferative (MIB-1 labeling) index, portal fibroinflammation, or ductal plate malformation. The loss of cilia did not correlate with the clinical follow-up in cases of pediatric CC. The loss of primary cilia from the intrahepatic cholangiocytes may be crucial in the etiopathogenesis of pediatric CC.

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

“…13 The cytoplasmic positivity of the primary ciliary protein with acetylated-α-tubulin antibody has previously been documented by us. 13 A few authors have previously documented cytoplasmic positivity with acetylated-α-tubulin antibody and correlated this positivity with the tumor prognosis in other non-UC tumors. 16,17 However, we could not document any correlation of cytoplasmic positivity of acetylated-α-tubulin with other prognostic parameters.…”

“…We have successfully used this ratio previously as well as in the index study 13 . The cytoplasmic positivity of the primary ciliary protein with acetylated-α-tubulin antibody has previously been documented by us 13 . A few authors have previously documented cytoplasmic positivity with acetylated-α-tubulin antibody and correlated this positivity with the tumor prognosis in other non-UC tumors 16,17 .…”

“…This ratio is unaffected by the cellular density and reflects an absolute number. We have successfully used this ratio previously as well as in the index study 13 . The cytoplasmic positivity of the primary ciliary protein with acetylated-α-tubulin antibody has previously been documented by us 13 .…”

“…The PC are also crucial for the cell-cell and cell-matrix interaction thereby maintaining cellular homeostasis in relation to its immediate vicinity. The dysfunction of the PC in terms of quantity and/or quality causes a group of congenital diseases with numerous developmental anomalies known as ciliopathies with an expanding spectrum 13 …”

“…The dysfunction of the PC in terms of quantity and/or quality causes a group of congenital diseases with numerous developmental anomalies known as ciliopathies with an expanding spectrum. 13 The role of the PC in tumor biology is only a recent topic of interest. They are hypothesized to be related to the biological behavior and propagation of the tumor.…”