The assessment of proliferating cell nuclear antigen immunohistochemical staining in small hepatocellular carcinoma and its relationship to histologic characteristics and prognosis

Abstract

Background. A precise prognostic factor for small hepatocellular carcinoma (HCC), the diagnosis of which recently has increased in incidence because of the development of diagnostic imaging techniques, is desirable. It has been reported that proliferating cell nuclear antigen (PCNA) would be related to proliferating cells, and thus the PCNA labeling index may provide useful information about the biologic behavior of small HCC. Methods. An assessment was made of proliferative activity by immunohistochemical staining using a monoclonal antibody against PCNA in 46 nodules of HCC less than 3 cm in diameter resected from 44 patients. A correlation between PCNA labeling index and clinicopathologic findings or prognosis was sought. Results. The mean labeling index was 18.7% in HCC and 1.9% in nontumor liver tissue. The labeling index corresponded to the degree of histologic differentiation, and the labeling index of well differentiated HCC was significantly lower (P < 0.05) than that of moderately or poorly differentiated HCC. The incidence of capsule formation in the high labeling index group (labeling index ± 20%) was significantly higher (P < 0.05) than that in the low labeling index group (labeling index < 20%). A high incidence of capsular and vascular invasion was found in the high labeling index group. The survival rate after resection was significantly higher (P < 0.05) and the recurrence rate significantly lower (P < 0.05) in the low labeling index group than in the high labeling index group. Conclusions. The PCNA labeling index was shown to be closely related to histologic characteristics, and proved to be a useful indicator of recurrence and survival in small HCC.

Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness

“…The high labeling index of PCNA results in high risk of tumor recurrence, more aggressive growth and poor survival (Kitamoto et al, 1993). MMP-9 gene is found to be highly expressed in HCC with invasive potential (Arii et al, 1996).…”

Hepatitis B virus-DNA level and basal core promoter A1762T/G1764A mutation in liver tissue independently predict postoperative survival in hepatocellular carcinoma

“…With the help of effective statistical methods, several molecules capable of predicting postoperative survival have been identified, such as proline-directed protein kinase F(A), MKP-1 (a mitogen-activated protein kinase), vascular endothelial growth factor, proliferating cell nuclear antigen, p53, TA (tissue factor), cytokeratin-19, telomerase activity, and interleukin-10. [14][15][16][17][18][19][20][21][22] Supposedly, these molecules are tightly linked to hepatocarcinogenesis and are therefore candidates for targeted therapy. In HBV-associated HCC, several virological factors have also been demonstrated to regulate cancer cell growth in both cell-based and animal-based studies.…”

Cell motility mediated by rho and rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma

“…6 A clinicopathological study showed that intrahepatic metastatic tumors develop more frequently in cases of HCC with a replacing or infiltrative growth component than in cases without such a component. 7 Proliferating cell nuclear antigen expression by HCCs seems to be related to tumor invasiveness and the prognosis, 8,9 and the nuclear DNA content of the tumor cells correlates with the postoperative recurrence of HCC. 10 Several chromosomal alterations appear to be responsible for the development of human HCC, 11,12 especially loss of heterozygosity of chromosome 16, which is detected at a higher rate in HCCs with intrahepatic metastasis and portal vein tumor thrombi.…”