Expression of AID, P53, and Mlh1 proteins in endoscopically resected differentiated-type early gastric cancer.
OBJECTIVE
To analyze the expression of the tumor-related proteins in differentiated-type early gastric carcinoma (DEGC) samples.


METHODS
Tumor specimens were obtained from 102 patients (75 males and 27 females) who had received an endoscopic tumor resection at Tottori University Hospital between 2007 and 2009. Ninety-one cancer samples corresponded to noninvasive or intramucosal carcinoma according to the Vienna classification system, and 11 samples were submucosal invasive carcinomas. All of the EGCs were histologically differentiated carcinomas. All patients were classified as having Helicobacter pylori (H. pylori) infections by endoscopic atrophic changes or by testing seropositive for H. pylori IgG. All of the samples were histopathologically classified as either tubular or papillary adenocarcinoma according to their structure. The immunohistochemical staining was performed in a blinded manner with respect to the clinical information. Two independent observers evaluated protein expression. All data were statistically analyzed then.


RESULTS
The rates of aberrant activation-induced cytidine deaminase (AID) expression and P53 overexpression were both 34.3% in DEGCs. The expression of Mlh1 was lost in 18.6% of DEGCs. Aberrant AID expression was not significantly associated with P53 overexpression in DEGCs. However, AID expression was associated with the severity of mononuclear cell activity in the non-cancerous mucosa adjacent to the tumor (P = 0.064). The rate of P53 expression was significantly greater in flat or depressed tumors than in elevated tumors. The frequency of Mlh1 loss was significantly increased in distal tumors, elevated gross-type tumors, papillary histological-type tumors, and tumors with a severe degree of endoscopic atrophic gastritis (P < 0.05).


CONCLUSIONS
Aberrant AID expression, P53 overexpression, and the loss of Mlh1 were all associated with clinicopathological features and gastric mucosal alterations in DEGCs. The aberrant expression of AID protein may partly contribute to the induction of nuclear P53 expression.
Yohei Takeda, Kazuo Yashima, Akihiro Hayashi, Shuji Sasaki, Koichiro Kawaguchi, Kenichi Harada, Yoshikazu Murawaki, Division of Medicine and Clinical Science, Faculty of Medicine, Tottori University, 36-1 Nishicho, Yonago 683-8504, Japan.
Yohei
Y
Takeda
Kazuo
K
Yashima
Akihiro
A
Hayashi
Shuji
S
Sasaki
Koichiro
K
Kawaguchi
Kenichi
K
Harada
Yoshikazu
Y
Murawaki
Hisao
H
Ito