Correlation between hcv-ns3p and p53, p21waf, mdm2, p21ras, and c-erbb2 in HVC associated hepatocellular carcinoma and adjacent pericarcinomatous foci

Abstract EN

Purpose : The non-structural protein 3 (NS3P) of HCV genome was linked to the neoplastic transformation of normal hepatocytes in chronically infected patients.

However, the exact mechanisms involved in this process are unidentified yet especially in the Egyptian population where genotype 4 represents the commonest type.

Patients and Methods : we investigated 32 HCV RT-PCR positive hepatocellular carcinoma (HCC) and 18 adjacent pericarcinomatous (PC) foci for the correlation between HCV- NS3P, p53, p21waf, mdm2, p21 ras and c-erbB2 and DNA content.

Results : NS3P expression was lower in HCC (65.6 %) than in PC (94.4 %).

The expression level of studied genes in HCC was: p53 (56.25 %), p21 waf (43.7 %), mdm2 (59.4 %), p21 ras (73.3 %) and c-erbB2 (75%).

In PC it was 22.2 %, 61.1 %, 44.4 %, 41.2% and 77.8 % respectively.

NS3P expression showed a significant correlation with the tumor grade, the presence of cirrhosis and chronic active hepatitis (CAH) (p < 0.05).

Overexpression of c-erbB2 and absence of p21 waf were higher in PC than in carcinomatous foci however, this did not reach a statistically significant level.

There was no correlation between NS3P and any of the studied genes in HCC however there was a strong positive correlation between NS3P, c-erbB2 and p21 waf (p < 0.01) in the PC.

There was a significant correlation between absence of p21 waf and CAH (p = 0.01) as well as between mdm2, c-erbB2 and cirrhosis (p = 0.025 and 0.001) in HCC cases.

There was a statistically significant difference in the ploidy status between HCC and PC (p < 0.05), however there was no significant relation between the ploidy status and other clinicopatholoogical features.

Conclusion : NS3P may exert its carcinogenic effect at an early stage of HCC possibly through a pathway involving c-erbB2 and p21 waf alterations.

On the other hand, p53, p21ras and mdm2 alterations are late events in this genetic cascade and are usually associated with worse differentiation and an aggressive behavior.