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Author Woo Sung Moon, Ho Sung Park, Ho Lee, Rama Pai, Andrzej S. Tarnawski, Kyung Ryoul Kim, Kyu Yun Jang
Place of duty Department of 1Pathology, 2Forensic Pathology, Chonbuk National University, Medical School and Center for Healthcare Technology Development, Jeonju, Korea, 3Department of Medicine, Veterans Administration Medical Center, Long Beach, California and the University of California, Irvine, California.
Title Co-Expression of Cox-2, C-Met and beta-catenin in Cells Forming Invasive front of Gallbladder Cancer
Publicationinfo Cancer Res Treat. 2005 Jun; 037(03): 171-176.
Key_word Gallbladder neoplasms,Immunohistochemistry,Cyclooxygenase 2,Proto-Oncogene Protein c-met,Beta catenin
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Abstract Purpose: Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E2 (PGE2), generated by cyclooxygenase 2 (Cox-2), transactivates epidermal growth factor receptor (EGFR), c-Met and beta-catenin; thus, enhancing colon cancer cell growth and invasiveness in vitro. To determine whether these findings are applicable to clinical conditions, we examined the expression and cellular localization/co-localization of Cox-2, c-Met, beta-catenin, EGFR and c-erbB2 in gallbladder cancer. Materials and Materials and Methods: Thirty-five specimens of invasive gallbladder cancer, 8 in situ carcinoma and 7 adenoma specimens were immunostained with specific antibodies against Cox-2, c-Met, beta-catenin, EGFR and c-erbB2. The cellular distribution, localization and co- localization were examined, and the signal intensities quantified in: a) the central area of gallbladder cancer and b) cancer cells forming the invasive front. Results: Cox-2, c-Met, beta-catenin, c-erbB2 and EGFR were over-expressed in 80, 74, 71, 62 and 11% of invasive gallbladder cancers, respectively. beta-catenin was expressed in 80% of non-malignant specimens, exclusively in the cell membrane, while the cancer specimens showed cytoplasmic and/or nuclear staining. Significantly higher Cox-2, c-Met and beta-catenin expressions were present in cancer cells of the invasive front than in the tumor central areas (p<0.001), and these expressions were significantly (p=0.01) associated with the invasion depth. Co- expressions of Cox-2, c-Met, beta-catenin and c-erbB2 were present in 42% of the specimens in cancer cells forming the invasive front. Conclusion: The overexpressions, and often co-localizations, of Cox-2, c-Met and beta-catenin in cancer cells forming the invasive front indicate their local interactions and important roles in invasion. (Cancer Res Treat. 2005; 37:171-176)