Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer

Futoshi Kawamata, Hirofumi Kamachi, Takahiro Einama, Shigenori Homma, Munenori Tahara, Masaya Miyazaki, Shinya Tanaka, Toshiya Kamiyama, Hiroshi Nishihara, Akinobu Taketomi, Satoru Todo

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25 Citations (Scopus)

Abstract

Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarcinoma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EHBDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization.

Original languageEnglish
Pages (from-to)2109-2118
Number of pages10
JournalInternational journal of oncology
Volume41
Issue number6
DOIs
Publication statusPublished - 2012 Dec 1
Externally publishedYes

Keywords

  • Intracellular localization
  • Luminal membrane expression
  • Mesothelin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kawamata, F., Kamachi, H., Einama, T., Homma, S., Tahara, M., Miyazaki, M., Tanaka, S., Kamiyama, T., Nishihara, H., Taketomi, A., & Todo, S. (2012). Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer. International journal of oncology, 41(6), 2109-2118. https://doi.org/10.3892/ijo.2012.1662