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The Korean Journal of Pathology 2005;39(6): 385-390.
Expression of Epidermal Growth Factor Receptor Related Protein in Gallbladder Cancer: An Association with p53 Mutation.
Ho Sung Park, Kyu Yun Jang, Kyung Ryoul Kim, Hak Yong Lee, Andrzej S Tarnawski, Adhip P N Majumdar, Myoung Jae Kang, Dong Geun Lee, Woo Sung Moon
1Department of Pathology, Chonbuk National University, Medical School, Korea. mws@chonbuk.ac.kr
2Center for Healthcare Technology Development, Jeonju, Korea.
3Department of Medicine, Veterans Administration Medical Center, Long Beach, California, and the University of California, Irvine, California, USA.
4John D. Dingle VA Medical Center, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
ABSTRACT
BACKGROUND: It has been well demonstrated that the overexpression of epidermal growth factor receptor (EGFR) is associated with numerous gastrointestinal malignancies, including gallbladder carcinoma. However, the cellular events that regulate EGFR in cancer cells have not been fully elucidated. A novel negative regulator of EGFR that is referred to as EGFR related protein (ERRP) has recently been identified. The aim of this study was to investigate the expression and localization of ERRP in gallbladder carcinoma and to examine a possible role for ERRP. METHODS: We examined the immunohistochemical expressions of ERRP, p53 and proliferating cell nuclear antigen labeling index (PCNA-LI) in formalin-fixed, paraffinembedded specimens of 43 cases of gallbladder carcinoma, 7 cases of adenoma and 3 cases of dysplasia. RESULTS: In the normal mucosa, ERRP immunoreactivity was positive in over 64% of specimens. In contrast, the ERRP staining was positive in only 46% of the cancer specimens. The expression of ERRP in cancer cells was inversely correlated with tumor cell proliferation. The loss of ERRP expression correlated with the p53 overexpression. CONCLUSIONS: Our data indicate that the down-regulation or loss of ERRP could play an important role in the progression of gallbladder carcinoma. The inverse relationship between the ERRP expression and PCNA-LI suggests that ERRP may play a role in the inhibition of tumor cell proliferation in gallbladder cancer.
Key Words: Gallbladder neoplasms; Epidermal growth factor receptor; Protein p53