Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

Abstract

In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC. © 2001 Cancer Research Campaign www.bjcancer.com

Crosstalk between EGFR and p53 in Hepatocellular Carcinoma

“…In our research, overexpression of p53 was found in 44% of HCCs. Our study showed that p53 overexpression was significantly associated with the poor histological differentiation of the tumor cells (p=0.008), which is consistent with previous reports (Ito et al, 2001;Qin et al, 2001;Lee et al, 2002;Sung et al, 2005).…”

“…EFGR inhibitors are promising therapeutic targets (Ito et al, 2001;Rampone et al, 2009;Berasain et al, 2011). Several EGFR agents such cetuximab panitumumab, gefitinib and erlotinib gained U.S. Food and Drug Administration (FDA) approval in recent years for different cancers (Bassullu et al, 2012).…”

“…In vitro, examination of EGFR inhibitors effects on HCC cells lines, demonstrated that they induce cell cycle arrest, apoptosis and increased the sensitivity to chemotherapy (Ito et al, 2001). Some studies conclude that the anti-EGFR agents have no effective response in patients with HCC (Bonner et al, 2010), while other have shown therapeutic effects in patients in a phase II clinical trial (Heesue et al, 2011).…”

“…For patients with early HCC that may benefit from liver resection, the survival rate at 5 years increased to 51.8% (Zhou et al, 2013). Unfortunately, most of the patients with HCC present in a late stage disease, when the treatment options are limited to chemoembolization or to systemic chemotherapy (Ito et al, 2001). The efficacy of the conventional cytotoxic drugs is poor and new therapeutic targets are imperative.…”

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…The receptors EGFR/ErbB-1 (Nakopoulou et al, 1994;Kira et al, 1997;Ito et al, 2001b), neu/Her2/ ErbB-2 (Nakopoulou et al, 1994;Ito et al, 2001b), Her3/ErbB-3 (Ito et al, 2001b) and Her4/ErbB-4 (Ito et al, 2001b) are expressed in HCCs; however, staining frequency and intensity of the tumor tissues in comparison to the surrounding non-tumorous liver tissues differ between these studies (Table 1). It is noteworthy that in contrast to other carcinomas (e.g.…”