Article Text

Download PDFPDF
Strong cytoplasmic expression of COX2 at the invasive fronts of gallbladder cancer is associated with a poor prognosis
  1. Haeryoung Kim1,
  2. Joo-Yeon Song1,3,
  3. Jai Young Cho2,
  4. Yoo-Seok Yoon2,
  5. Ho-Seong Han2,
  6. Hye Seung Lee1,
  7. Han Suk Ryu1,
  8. Gheeyoung Choe1
  1. 1Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea
  2. 2Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
  3. 3Department of Pathology, Dongnam Institute of Radiological … Medical Sciences Cancer Center, Busan, South Korea
  1. Correspondence to Dr Gheeyoung Choe, Department of Pathology, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, South Korea; gychoe{at}


Aim The significance of cell cycle proteins, p21 and p53, and cyclo-oxygenase-2 (COX2) is still controversial in gallbladder adenocarcinoma. Conflicting results exist with regard to the prognostic significance of p21 and p53 expression, and the strong association of gallbladder cancer with chronic inflammation makes it only natural that COX2 negativity is rarely encountered, even in non-neoplastic biliary epithelia.

Methods The authors explored whether the p21 and p53-labelling indices (LI) and strong cytoplasmic COX2 expression differ in the central parts (TC) and invasive fronts (IF) of gallbladder cancer. Paraffin-embedded whole tissue sections of 67 gallbladder cancers were immunohistochemically analysed for p21, p53 and COX2-LI at the IF and TC, and results were correlated with the clinicopathological features.

Results Significantly higher LI was seen in IF compared with TC for p21, p53 and COX2. COX2-LI-IF showed significant positive correlations with perineural and lymphatic invasion, higher T and N stages, and non-papillary gross morphology. Gall-bladder cancers with COX2-LI-IF≥30% showed decreased overall and disease-free survival, and COX2-LI-IF≥30% was an independent poor prognostic factor on multivariable analysis. Gall-bladder cancers with high COX2 and p21-LI-IF showed decreased overall and disease-free survival.

Conclusions The IF of gallbladder cancer is characterised by significantly increased expression of p21, p53 and strong COX2 expression, and strong cytoplasmic COX2 expression at IF is associated with a poorer prognosis. Heterogeneity between TC and IF should be considered in in situ molecular studies, especially during interpretation of immunohistochemical stain results and tissue microarray construction.

  • Gall-bladder cancer
  • COX2
  • invasive front
  • prognosis

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding This work was partly supported by a grant from the SNUBH Research Fund (grant number: 11-2009-008).

  • Competing interests None.

  • Ethics approval This study was approved by the Research Ethics Committee (Institutional Review Board: B-0912/090-302) of Seoul National University Bundang Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.