Reduced expression of epidermal growth factor receptor-related protein in hepatocellular carcinoma: implications for cancer growth.
OBJECTIVE
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.
Moon
Woo Sung
WS
Department of Medicine, VA Medical Center, Long Beach and The University of California, Irvine, CA 90822-5201, USA.
Chang
Kenneth J
KJ
Majumdar
Adhip P N
AP
Tarnawski
Andrzej S
AS
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000503:physiopathology*; D002455:Cell Division; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016158:Genes, p53; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D008969:Molecular Sequence Data; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors