Intracellular localization of mesothelin predicts patient prognosis             of extrahepatic bile duct cancer.
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 adenocarci-noma, 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.
Department of General Surgery, Hokkaido University School of                     Medicine, Sapporo 060-8638, Japan.
Futoshi
F
Kawamata
Hirofumi
H
Kamachi
Takahiro
T
Einama
Shigenori
S
Homma
Munenori
M
Tahara
Masaya
M
Miyazaki
Shinya
S
Tanaka
Toshiya
T
Kamiyama
Hiroshi
H
Nishihara
Akinobu
A
Taketomi
Satoru
S
Todo
D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D021381:Protein Transport
D058851:GPI-Linked Proteins; D000090204:Mesothelin