title: Co-expression of cox-2, C-met and beta-catenin in cells forming invasive front of gallbladder cancer.
abstract: OBJECTIVE
  Gallbladder cancer is a malignancy with poor prognosis, predominantly resulting from invasion and metastasis. Our previous studies have demonstrated that prostaglandin E(2) (PGE(2)), 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.
  
  
  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 colocalization 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology, Chonbuk National University, Medical School and Center for Healthcare Technology Development, Jeonju, Korea. mws@chonbuk.ac.kr
authors: Woo Sung
authors: WS
authors: Moon
authors: Ho Sung
authors: HS
authors: Park
authors: Ho
authors: H
authors: Lee
authors: Rama
authors: R
authors: Pai
authors: Andrzej S
authors: AS
authors: Tarnawski
authors: Kyung Ryoul
authors: KR
authors: Kim
authors: Kyu Yun
authors: KY
authors: Jang