Both Fibrous Capsule Formation and Extracapsular Penetration Are Powerful Predictors of Poor Survival in Human Hepatocellular Carcinoma: a Histological Assessment of 365 Patients in Japan

Background: A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series.

Methods: A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule.

Results: The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482).

Conclusions: Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.