Cytokeratin 19 Expression in Hepatocellular Carcinoma Predicts Early Postoperative Recurrence

Clinicopathologic features and postoperative outcomes were investigated for patients who underwent curative surgery for biliary marker (CK7 and CK19)-positive hepatocellular carcinoma (HCC). Of 157 HCCs, 93 were CK7(-)CK19(-), 49 were CK7(+)-CK19(-), 1 was CK7(-)CK19(+), and 14 were CK7(+)- CK19(+). Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness.