Clinical significance of dysadherin expression in gastric cancer patients.
OBJECTIVE
Dysadherin, a cancer-associated cell membrane glycoprotein, has been reported to down-regulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in gastric cancer, we examined dysadherin and E-cadherin expression in gastric cancer patients.


METHODS
Dysadherin and E-cadherin expression were evaluated in 276 gastric cancer patients by immunohistochemistry, and the results were compared with the clinicopathological findings of the subjects.


RESULTS
Dysadherin was not expressed in normal gastric epithelium. Both dysadherin and E-cadherin were localized to the cell membrane. Dysadherin expression was sometimes largely localized to infiltrating tumor cells or cells dissociating. Ninety gastric cancer patients (32.6%) were positive for dysadherin, and 151 patients (54.7%) showed preservation of E-cadherin expression. Expression of dysadherin was associated with moderately differentiated carcinoma and hematogenous metastasis, whereas reduced expression of E-cadherin showed an association with poorly differentiated carcinoma and peritoneal dissemination. As a result, dysadherin positivity and reduced E-cadherin expression were associated with a poor prognosis. In addition, patients with both dysadherin positivity and reduced E-cadherin had the worst prognosis. Multivariate analysis revealed that reduced E-cadherin expression was an independent prognostic factor, but dysadherin expression was not.


CONCLUSIONS
Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis and the mode of metastasis in gastric cancer patients. Patients with dysadherin positivity have a higher risk of hematogenous metastasis, whereas patients with reduced E-cadherin expression have an increased risk of peritoneal dissemination.
Shimada
Yutaka
Y
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan. shimada@kuhp.kyoto-u.ac.jp
Yamasaki
Seiji
S
Hashimoto
Yosuke
Y
Ito
Tetsuo
T
Kawamura
Jun-ichiro
J
Soma
Toshiya
T
Ino
Yoshinori
Y
Nakanishi
Yukihiro
Y
Sakamoto
Michiie
M
Hirohashi
Setsuo
S
Imamura
Masayuki
M
D000368:Aged; D015820:Cadherins / Q000096:biosynthesis* / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007473:Ion Channels; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D008840:Microfilament Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism*; D013997:Time Factors
D015820:Cadherins; C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins