Utility of Cell-cycle Modulators to Predict Vascular Invasion and Recurrence After Surgical Treatment of Hepatocellular Carcinoma

Abstract

The outcome of surgical treatment of hepatocellular carcinoma (HCC) could be improved by applying patient selection criteria based on tumoral aggressiveness. Here we analyzed the prognostic role of the expression of several genes involved in cell-cycle regulation in a group of patients with HCC. We retrospectively studied 93 patients (67 transplanted and 26 resections) treated between 1996 and 2000. In micro-thick sections from paraffin-embedded tumoral tissues, the expression of p53, pRb, p16, and cyclin D1 was analyzed. A logistic regression model was used to detect factors related to vascular invasion. A Cox regression model was applied to identify pathologic and molecular factors with the capacity to predict the recurrence of HCC. Only tumor size>3 cm (odds ratio [OR]: 3.4; 95% CI: 1.2-9.9; P=0.019) and pRb expression (OR: 4.1; 95% CI: 1.02-17; P=0.053) were associated with an increased risk of vascular invasion. The regression model applied to the group of transplanted patients showed three factors that were independently related to recurrence: vascular invasion (OR 7.5; 95% CI: 1.1-51.8; P=0.039); pRb expression (OR: 11; 95% CI: 1.2-96.9; P=0.03); and p16 expression (OR: 69.7; 95% CI: 5.1-9448; P=0.001). In the group of resected patients, pRb expression was associated with higher risk of recurrence only in the univariate analysis (P=0.037). The multivariate analysis showed tumor size>3 cm (OR: 57.5; 95% CI: 1.1-51.8; P=0.039) and vascular invasion (OR: 6.1; 95% CI: 1.05-35.3; P=0.044) to be significantly associated with recurrence. Of the molecular factors studied, only pRb expression was useful as a predictive factor of vascular invasion in patients with HCC, and also of recurrence in transplanted patients with this carcinoma. pRb expression may be relevant to consider when selecting patients for resection and when identifying transplanted patients with a high risk of recurrence.