Reduced expression of epidermal growth factor receptor-related protein in hepatocellular carcinoma: implications for cancer growth.

BACKGROUND/AIMS: The mitogenic signaling pathway of epidermal growth factor receptor (EGFR) is activated in a variety of cancers, including hepatocellular carcinoma (HCC). The recently cloned EGFR-related protein (ERRP) has been proposed to be a negative regulator of EGFR. The expression of ERRP in non-malignant liver cells and in HCC, and its relation to cell proliferation, have not been examined.

METHODS

Paraffin sections of formalin-fixed HCC specimens of 51 HCCs and 10 normal liver specimens were immunostained with anti-ERRP and anti-p53 antibodies. To determine the relationship between ERRP expression and cell proliferation, we performed double staining for ERRP and proliferating cell nuclear antigen (PCNA) in the same HCC specimens.

RESULTS

In normal liver, ERRP was expressed in 100% of specimens, while in non-malignant liver tissue from HCC, ERRP expression was present in 50% of the specimens (p < 0.001). In contrast, ERRP expression was present only in 14% of the HCC specimens. The expression of ERRP in cancer cells was inversely correlated with proliferative activity and tumor size (p < 0.001, p < 0.05, respectively). No significant correlation was found between p53 expression and the expression of ERRP.

CONCLUSIONS

Human HCC, which has been shown to be associated with increased activation of EGFR, exhibits a substantial reduction in ERRP expression. The inverse relationship between ERRP expression, proliferative activity of tumor cells and tumor size suggests that in some HCC, ERRP is a negative regulator of HCC growth.