Clinicopathological Significance of Osteopontin in Cholangiocarcinoma Cases

Abstract

Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients.

Figure 1. Immunohistochemical Staining of OPN in CCA Cells and Stromal Tissue

A) normal portal triads of the liver shows no OPN expression in bile duct epithelium and stroma, B) negative OPN in cancer cells and stroma, C) negative OPN in cancer cells but positive in stroma, and D) positive OPN expression in both cancer cells and stroma. Immunoperoxidase staining, original magnification x100 (A) and x200 (B, C and D)

Figure 2. Kaplan-Meier Survival Analysis of OPN Expression in CCA Cells (A) and Stroma (B)

OPN expression either in carcinoma cells or stroma shows no influence in patients’ survival (P>0.05)