Different roles of S100P Overexpression in Intrahepatic Cholangiocarcinoma

Abstract

S100P is expressed in several kinds of malignant tumors. Intracellular S100P interacts with ezrin, and extracellular S100P activates the receptor for advanced glycation endproducts. However, little is known about the biological significance of S100P and related proteins in cholangiocarcinoma. Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar or perihilar cholangiocarcinoma. We examined S100P, ezrin, and the receptor for advanced glycation end product expression in 39 BilIN and 110 intrahepatic cholangiocarcinoma (ICC) cases, and analyzed its relationship with clinicopathologic factors and outcomes. S100P expression increased from reactive epithelium to low-grade BilIN to high-grade BilIN. S100P and ezrin expression rates in perihilar-type ICC were higher than those in peripheral-type ICC (P<0.0001, P=0.0008, respectively). S100P nuclear expression in peripheral-type ICC significantly correlated with vascular invasion (P=0.0209), lymphatic invasion (P=0.0003), and lymph node metastasis (P=0.003). S100P and ezrin expression was significantly correlated. S100P-positive and ezrin-positive cases indicate shorter survival in survival analysis of the peripheral type (P=0.001, P=0.0728, respectively). Our results suggest that S100P-ezrin signaling has different roles of carcinogenesis of perihilar ICC and an aggressive course of peripheral ICC.

S100P Expression Is a Novel Prognostic Factor in Hepatocellular Carcinoma and Predicts Survival in Patients with High Tumor Stage or Early Recurrent Tumors

“…The S100P protein was first identified in the human placenta [23], and has been reported to be overexpressed in multiple types of cancer cells, including breast cancer [13], [24], esophageal cancer [15], colon cancer [19], lung cancer [25], pancreatic cancer [26], [27], prostatic cancer [28], ovarian cancer [29], cholangiocarcinoma [30]–[32], and HCC [33]. However, the clinical and pathological significance of S100P expression in human HCC remains unclear.…”

Prognostic Value of Ezrin in Solid Tumors: A Meta-Analysis of the Literature

“…The total number of patients included for meta-analysis was 4693, ranging from 40 to 487 per study. In total, 22 studies had data on OS [6], [7], [8], [10], [11], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], and 7 study have data on DFS [6], [9], [23], [33], [34], [35], [36]. 13 reports originated from Asia, 14 from Non Asia.…”

The diagnostic and prognostic value of MRP8/MRP14 in intrahepatic cholangiocarcinoma

“…There is increasing interest in the S100 proteins and their relationship with inflammatory bile duct diseases [ 22 ], BilIN and ICC [ 23 ], as well as both malignant and benign gallbladder diseases [ 24 ], because of their altered expression in various malignancies. In a recent study, the prognostic significance of S100A4 in ICC was evaluated [ 25 ].…”

“…Hematoxylin and eosin (H&E)-stained slides made from each formalin-fixed paraffin-embedded tissue that had undergone surgical resection were reviewed by two experienced hepatopathologists (WM Cong and H Dong). IHBD was defined as the mildly hyperplastic epithelium with intraepithelial neutrophils and lymphocytic infiltration, lacking a definite disturbance of cell polarity [ 23 ]. The histopathologic definition of BilIN was based on the classification proposed by Zen et al [ 30 ].…”