Expression of epithelial cell adhesion molecule associated with elevated ductular reactions in hepatocellar carcinoma.

AIM: To evaluate the prognostic significance of the epithelial cell adhesion molecule (EpCAM) expression in HCC, the relationship between EpCAM with ductular reactions and other clinical features. METHODS: From 2001 to 2003, 106 HCC patients who underwent curative resection in Eastern Hepatobiliary Hospital were enrolled. The expression of EpCAM in tumoral tissues and ductular reactions in paired non-tumoral tissues was assessed by immunohistochemistry. EpCAM was evaluated with prognosis, ductular reactions and other clinical variables. RESULTS: HCC expressing high level of EpCAM showed more aggressively than usual progressed HCC. High EpCAM expression was associated with poor overall survival and recurrence free survival. (P=0.0005, 0.0019, respectively). A close association was found between tumoral EpCAM expression and peritumoral ductular reactions. Patients with high level of ductular reactions tended to have higher EpCAM expression than those with low level (P=0.016). CONCLUSION: HCC stratification by EpCAM may reflect different prognosis. EpCAM expression correlated with ductular reactions may be a result of unregulated activation and differentiation blockage of progenitor cells.

Peritumoral ductular reaction: a poor postoperative prognostic factor for hepatocellular carcinoma.

BACKGROUND: The role of ductular reaction (DR) in hepatocellular carcinoma (HCC) remains to be elucidated. METHODS: In this study, we tried to uncover possible effect by correlating peritumoral DR in a necroinflammatory microenvironment with postoperative prognosis in HCC. The expression of peritumoral DR/CK19 by immunohistochemistry, necroinflammation and fibrosis were assessed from 106 patients receiving curative resection for HCC. Prognostic values for these and other clinicopathologic factors were evaluated. RESULTS: Peritumoral DR significantly correlated with necroinflammation (r = 0.563, p = 3.4E-10), fibrosis (r = 0.435, p = 3.1E-06), AFP level (p = 0.010), HBsAg (p = 4.9E-4), BCLC stage (p = 0.003), TNM stage (p = 0.002), multiple nodules (p = 0.004), absence of tumor capsule (p = 0.027), severe microscopic vascular invasion (p = 0.031) and early recurrence (p = 0.010). Increased DR was significantly associated with decreased RFS/OS (p = 4.8E-04 and p = 2.6E-05, respectively) in univariate analysis and were identified as an independent prognostic factor (HR = 2.380, 95% CI = 1.250-4.534, p = 0.008 for RFS; HR = 4.294, 95% CI = 2.255-8.177, p = 9.3E-6 for OS) in multivariate analysis. CONCLUSIONS: These results suggested that peritumoral DR in a necroinflammatory microenvironment was a poor prognostic factor for HCC after resection.

Background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma.

UNLABELLED: Hepatic progenitor cells (HPC) play important roles in both liver regeneration and carcinogenesis. Combined hepatocellular-cholangiocarcinoma (CHC), a malignant primary liver tumor with poor prognosis, is thought to be of HPC origin. However, the prognostic significance of this etiology is not well defined. Therefore, we retrospectively investigated the relationship of HPC-related pathological features and long-term outcome in patients with CHC in our department. In a cohort of 80 patients identified between 1997 and 2003, including 70 patients who underwent resection with curative intent, overall survival (OS) and disease-free survival (DFS) were correlated with the proliferative activity of nontumor ductular reaction (DR) and the expression levels of HPC and biliary markers including α-fetoprotein (AFP), keratin 7 (K7), keratin 19 (K19), oval cell (OV)-6, epithelial cell adhesion molecule (EpCAM), and c-Kit in both tumor and nontumor liver. We found that nontumor ductular reactions (DRs), specifically the proliferating cell nuclear antigen (PCNA) labeling index of the ductular reaction (PI-DR), a surrogate for transit-amplifying compartments, was an independent prognostic factor for both OS and DFS. By contrast, intratumoral expression of only one marker, absence of AFP, was associated with OS. PI-DR was also independently associated with synchronous "multicentric occurrence" in hepatocellular carcinoma components, a feature of CHC that may predispose to metachronous multifocal tumorigenesis. CONCLUSION: Proliferative ductular reaction related to HPC activation is associated with recurrence of CHC. Background HPC activation is strongly associated with multifocal occurrence and related tumor recurrence, highlighting the critical role of background liver disease, a "field effect," in the recurrence of CHC.