Oncogenic Wnt3a expression as an estimable prognostic marker for hepatocellular carcinoma

Abstract

Aim: To investigate member 3a of Wingless-type MMTV integration site family (Wnt3a) expression in cancerous and surrounding tissues and the relationship between clinicopathologic features of hepatocellular carcinoma (HCC) and Wnt3a expression.

Methods: Wnt3a expression and cellular distribution and clinicopathologic characteristics in cancerous tissue and matched surrounding tissues were analyzed in 80 HCC patients from January 2006 to August 2008 by tissue microarrays and immunohistochemistry. The overall and disease-free survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.

Results: The incidence of oncogenic Wnt3a expression in the cancerous group was up to 96.25% (77 of 80), which was significantly higher (χ(2) = 48.818, P < 0.001) than that in the surrounding group (46.25%, 37 of 80). Brown Wnt3a staining gradually increased with clinical staging that showed very strong staining in advanced HCC. The clinicopathologic features of high Wnt3a expression in HCC were related to poorly-differentiated grade (χ(2) = 20.211, P < 0.001), liver cirrhosis (χ(2) = 8.467, P < 0.004), hepatitis B virus (HBV) infection (χ(2) = 12.957, P < 0.001), higher tumor-node-metastasis stage (χ(2) = 22.960, P < 0.001), and 5-year survival rate (χ(2) = 15.469, P < 0.001).

Conclusion: Oncogenic Wnt3a expression associated with HBV infection and cirrhotic liver might be an independent prognostic factor for HCC.

Keywords: Hepatocellular carcinoma; Immunohistochemistry; Prognosis; Tissue microarrays; Wnt/β-catenin signal; Wnt3a.

Figure 1

Analysis of hepatic Wnt3a expression and its cellular distribution by immunohistochemistry. The expression of hepatic Wnt3a was analyzed on tissue microarrays by immunohistochemistry with the primary mouse anti-human Wnt3a antibody. The positive Wnt3a expression with brown staining particles was distributed in the cytosol and membrane of hepatocytes and only a few cell nuclei. A and B: Strong straining of Wnt3a in hepatocellular carcinoma (HCC) tissues; C and D: Light staining of Wnt3a in surrounding tissue. A and C: Original magnification × 400; B and D: Original magnification × 400.

Figure 2

Expression of hepatic Wnt3a at different hepatocellular carcinoma stages. A1 and B1: Low or no Wnt3a expression in the para-cancerous tissues. A2-A5 and B2-B5: The brown staining of Wnt3a gradually increases in cancerous tissues from stage I to IV. A1-A5: Original magnification × 200; B1-B5: Original magnification × 400.

Figure 3

Overall survival curves of 80 hepatocellular carcinoma patients. The Wnt3a expression curves were calculated by the Kaplan-Meier method. Survival curves of 80 hepatocellular carcinoma patients were made according to cancerous tissues expressing a low or high level of Wnt3a (log-rank test, P < 0.001). The green line is the high Wnt3a group; and the blue line is the low or without Wnt3a group.