Growth kinetic study of human hepatocellular carcinoma using proliferating cell nuclear antigen and Lewis Y antigen: their correlation with transforming growth factor-alpha and beta 1.

The factors which control the balance between proliferation and cell death in hepatocellular carcinoma (HCC) remain unclear. The kinetic state of the tumor growth was investigated in the present study with references to transforming growth factor (TGF)-alpha and -beta 1 in 50 resected HCCs without preceding therapies. three-micrometer sections were cut from formalin-fixed, paraffin-embedded tumors. Proliferating cell nuclear antigen (PCNA), Lewis Y antigen (LeY). TGF-alpha, and -beta 1 were immunohistochemically stained and quantitatively assessed with an image analyzer. By means of immunohistochemical staining, a reciprocal correlation was observed between PCNA and LeY. A similar pattern was found between TGF-alpha and -beta 1, although not so strikingly as in the case of PCNA and LeY. The expression of LeY and PCNA labeling index (LI) ranged from 0 to 56.1% and from 0 to 52.8%, respectively. A correlation was observed between LeY and tumor size (r = 0.302, p < 0.04), while there was no significant relationship between PCNA LI and tumor size (r = -0.048, p > 0.05). The positive area ranged from 0 to 61.6% for TGF-alpha, and from 0.6 to 71.5% for TGF-beta 1. Analysis of these data showed a significant correlation between TGF-beta 1 and tumor size (r = -0.327, p < 0.03). Among HCCs < 5 cm, PCNA LI positively correlated with tumor size (r = 0.399, p < 0.04), but negatively with TGF-beta 1 (r = -0.431, p < 0.03). In conclusion, the present investigation indicates that the simultaneous analyses of proliferating and apoptotic activities by means of PCNA and LeY could yield more accurate data to determine the kinetic state of the tumor growth compared with either alone. In addition, TGF-beta 1 might act as a suppressive factor in the growth of HCC < 5 cm.