Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocarcinoma

Background Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and alpha-smooth muscle actin were performed in tumor and peritumor liver tissues. Results A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r=0.357, 95% CI, 0.037-0.557; P=0.008 and r=0.742, 95% CI, 0.580-0.849; P< 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P=0.058) and poor overall and disease-free survival time (P=0.01 and P=0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43 +/- 0.29 vs 0.28 +/- 0.31, P=0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septal alpha-SMA level (r=0.359, P=0.001). Conclusions Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.