Decreased expression of CDH1 or CTNNB1 affects poor prognosis of patients with esophageal cancer.
BACKGROUND
E-cadherin/CDH1 is one of the proteins involved in cell adhesion, and it is known that decreased expression of E-cadherin induces lymph node metastasis in esophageal cancer. Beta catenin/CTNNB1, which is an important component of the Wnt signaling pathway, binds to E-cadherin at the cell membrane, where the complex of these two proteins functions in the stabilization of cell adhesion. However, its role in the pathogenesis of esophageal cancer is still unknown.


METHODS
This study included 86 patients with esophageal cancer who underwent surgery between 1998 and 2007. The expression of the E-cadherin/CDH1 gene product (E-cadherin/CDH1) and that of the beta catenin/CTNNB1 protein in the cell membrane were analyzed by immunohistochemistry. We examined the correlations among CDH1 or CTNNB1 expression, clinicopathological factors, and the prognosis of patients with ESCC.


RESULTS
CDH1 and CTNNB1 were expressed in 52.3 % (45/86) and 36.0 % (31/86) of tumor samples, respectively. Both CDH1 and CTNNB1 were co-expressed in 22.1 % (19/86) of esophageal cancer tissues. CDH1 expression correlated with the p-stage (stages I-II vs stages III-IV, p = 0.032), T factor (T1-2 vs T3-4, p = 0.0088), and lymphatic invasion (p = 0.019). However, CDH1 expression did not correlate with the N factor or the blood vessel invasion. CTNNB1 expression correlated with the T factor (T1-2 vs T3-4, p = 0.0015), p-stage (stages I-II vs stages III-IV, p = 0.030), and lymphatic invasion (p = 0.007). The CDH1(+)/CTNNB1(+) phenotype was inversely correlated with the T factor, N factor, p-stage, lymphatic invasion, and blood vessel invasion. Furthermore, patients whose tumors were double-positive for CDH1 and CTNNB1 had a significantly higher survival rate than those whose tumors were negative for CDH1 or CTNNB1 (log-rank test, p = 0.0192). The T factor and N factor had a strong negative correlation with double-positive tumors. These were both independent prognostic factors, as was the double-positive phenotype. A univariate analysis indicated that the T factor, the N factor, and CDH1 and CTNNB1 co-expression were significant variables that predicted survival (hazard ratio, 2.387; 95 % confidence interval, 1.115-5.102; p = 0.025).


CONCLUSIONS
Decreased expression of CDH1 or CTNNB1 in the cell membranes of cancer cells is associated with poor survival of patients with esophageal cancer.
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. h-ishi@med.nagoya-cu.ac.jp1.
Hideyuki
H
Ishiguro
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Takehiro
T
Wakasugi
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Yukio
Y
Terashita
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Nobuhiro
N
Sakamoto
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Tatsuya
T
Tanaka
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Koji
K
Mizoguchi
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Hiroyuki
H
Sagawa
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Tomotaka
T
Okubo
Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Hiromitsu
H
Takeyama
D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D051176:beta Catenin
CDH1-CTNNB1; Esophageal cancer; Immunohistochemistry; Prognosis