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.