Subclassification of Microscopic Vascular Invasion in Hepatocellular Carcinoma

Objective: To investigate whether subclassification of microscopic vascular invasion (MiVI) affects the long-term outcome after curative surgical resection or liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Summary of Background Data: The most important factor for TNM staging in HCC is MiVI, which includes all vascular invasions detected on microscopic examination. However, there is a broad spectrum of current definitions for MiVI. Methods: In total, 412 consecutive patients with HCC who underwent curative surgical resection without any preoperative treatment or gross vascular invasion were histologically evaluated for MiVI. Patients with MiVI were subclassified into 2 groups: microvessel invasion (MI; n = 164) only and microscopic portal vein invasion (MPVI; n = 36). Clinicopathologic features were compared between 2 groups (MI vs MPVI), whereas disease-free survival (DFS) and overall survival (OS) after resection were analyzed among 3 groups (no vascular invasion [NVI] vs MI vs MPVI). These subclassifications were validated in a cohort of 197 patients with HCC who underwent LT. Results: The MPVI group showed more aggressive tumor characteristics, such as higher tumor marker levels (alpha-fetoprotein, P = 0.006; protein induced by vitamin K absence-II, P = 0.001) and poorer differentiation ( P = 0.011), than the MI group. In multivariate analysis, both MI and MPVI were independent prognostic factors for DFS ( P = 0.001 and <0.001, respectively) and OS ( P = 0.005 and <0.001, respectively). In the validation cohort, 5-year DFS was 89%, 67.9%, and 0% in the NVI, MI, and MPVI groups, respectively ( P < 0.001), whereas 5-year OS was 79.1%, 55.0%, and 15.4%, respectively ( P < 0.001). Conclusions: Based on subclassification of MiVI in HCC, MPVI was associated with more aggressive clinicopathologic characteristics and poorer survival than MI only. Therefore, the original MiVI classification should be divided into MI and MPVI.