Frequent occurrence of abnormal E-cadherin/beta-catenin protein expression in advanced gallbladder cancers and its association with decreased apoptosis.
OBJECTIVE
Our aim is to assess the clinicopathological significance of E-cadherin and beta-catenin expression, as well as their association with apoptosis in gallbladder cancers.


METHODS
The expression of E-cadherin and beta-catenin proteins was examined in 4 biliary tract cancer cell lines and 49 gallbladder cancer specimens by immunofluorescent or immunohistochemical methods and Western blotting. The apoptotic status was evaluated in the cell lines by poly(ADP-ribose) polymerase Western blotting and in the tumors by the TdT-mediated dUTP nick end labeling assay.


RESULTS
Expression of poly(ADP-ribose) polymerase (apoptosis) was only seen in cell lines that expressed both E-cadherin and beta-catenin. Reduced expression of E-cadherin and beta-catenin was frequently seen in advanced gallbladder cancer cases (61 and 83%, respectively) relative to pT1 cases (25 and 63%, respectively). The 5-year survival rate in cases with reduced E-cadherin expression was 26%, significantly lower than in cases with preserved E-cadherin expression (70%; p = 0.017). Cases with reduced expression of both had lower apoptotic indices and showed a worse prognosis compared with cases with reduced expression of either E-cadherin or beta-catenin (p = 0.04 and 0.049, respectively).


CONCLUSIONS
The expression of E-cadherin or beta-catenin frequently diminishes as the tumor progresses, and abnormalities of E-cadherin and beta-catenin expression were associated with decreased apoptosis in gallbladder cancers. E-cadherin expression might be a useful prognostic marker in this tumor.
Hirata
Kenro
K
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Kobe, Japan.
Ajiki
Tetsuo
T
Okazaki
Taro
T
Horiuchi
Hideki
H
Fujita
Tsunenori
T
Kuroda
Yoshikazu
Y
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D015703:Antigens, CD; D017209:Apoptosis; D001661:Biliary Tract Neoplasms / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D005706:Gallbladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011379:Prognosis; D015996:Survival Rate; D051176:beta Catenin / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051176:beta Catenin; D011065:Poly(ADP-ribose) Polymerases