Expression and altered subcellular localization of the cyclin-dependent kinase inhibitor p27Kip1 in hepatocellular carcinoma

AIM: To investigate p27 expression in hepatocellular carcinoma (HCC), adjacent nontumoral and normal liver tissues, and to verify whether the subcellular localization of p27 was altered in HCC. METHODS: The level of p27 in tumoral, nontumoral, and normal liver tissues were assessed by immunohistochemical (IHC) analysis. Parallel immunostaining was done for proliferating cell nuclear antigen (PCNA) to evaluate cell proliferation. RESULTS: The labeling index (LI) of p27 in tumoral lesions was significantly lower than that in adjacent nontumoral lesions (t=2.444, P=0.017) and normal controls (t=2.268, P=0.029). The LI of p27 significantly decreased in patients with massive type (t=2.227, P=0.037) and infiltration (t=2.197, P=0.036). The prognosis of patients with higher p27 LI was longer than that of patients with lower p27 LI (P=0.0247, log-rank test). The LI of PCNA was significantly higher in HCC than that in adjacent nontumoral lesions (t=2.092, P=0.041) and normal controls (t=3.533, P=0.002). There was no significant correlation between p27 expression and cell proliferation in tumor samples. The level of p27 in the cytoplasmic fraction was higher in tumoral and nontumoral liver tissues, and was associated with clinical stage (t=2.520, P=0.029) and the degree of invasion (t=2.640, P=0.019). Survival analysis showed that p27 was an independent prognosis marker for HCC patients. CONCLUSION: These results suggest that p27 underexpressing in patients with HCC is closely associated with infiltration, metastasis, and prognosis. Alterations in the subcellular localization of p27 protein may occur early during hepatocarcinogenesis.