Co-Expression of Cox-2, C-Met and beta-catenin in Cells Forming Invasive front of Gallbladder Cancer.
- Author:
Woo Sung MOON
1
;
Ho Sung PARK
;
Ho LEE
;
Rama PAI
;
Andrzej S TARNAWSKI
;
Kyung Ryoul KIM
;
Kyu Yun JANG
Author Information
1. Department of Pathology, Chonbuk National University, Medical School and Center for Healthcare Technology Development, Jeonju, Korea. mws@chonbuk.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Gallbladder neoplasms;
Immunohistochemistry;
Cyclooxygenase 2;
Proto-Oncogene Protein c-met;
Beta catenin
- MeSH:
Adenoma;
Antibodies;
beta Catenin*;
Cell Membrane;
Colonic Neoplasms;
Cyclooxygenase 2;
Cytoplasm;
Dinoprostone;
Gallbladder Neoplasms*;
Gallbladder*;
Immunohistochemistry;
Neoplasm Metastasis;
Prognosis;
Receptor, Epidermal Growth Factor
- From:Cancer Research and Treatment
2005;37(3):171-176
- CountryRepublic of Korea
- Language:English
-
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 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.