Prognostic significance of the worst grade in hepatocellular carcinoma with heterogeneous histologic grades of differentiation

Background and Aim: Although tumor differentiation is a known prognostic factor after the treatment of hepatocellular carcinoma (HCC), there have not been any studies on the prognostic significance of tumor differentiation in HCC with heterogeneous histologic grades. In this study, we attempted to ascertain whether the major or the worst grade in mixed histologic type HCC determines the prognosis after liver resection. Methods: From January 1996 to March 2010, a total of 724 patients underwent curative resection of HCC at Yonsei University Health System, Korea. Of those, we excluded 99 patients who had total necrosis because of previous treatment. Among the remaining 625 patients, we compared the homogeneous moderately differentiated group (HG2, n=241), mixed histologic grades with the worst component as poorly differentiated group (M2, n=142), and homogeneous poorly differentiated group (HG3, n=156). The clinicopathologic features, disease-free survival (DFS) and overall survival (OS) in each group were analyzed. Results: The DFS and OS were significantly lower in M2 than in HG2 (P=0.004 and 0.025, respectively) whereas those of M2 were not significantly different from HG3. There were no significant differences in the clinicopathologic features of each group except that microvascular invasion was more frequently observed in M2 than in HG2. On multivariate analysis, being in the worst histologic group (M2 and HG3) was an independent poor prognostic factor for DFS and OS (P=0.028 and <0.001, respectively). Conclusions: In patients with advanced histologic grade, the worst histologic grade may determine the prognosis after curative resection of HCC.