Reduced MUTYH, MTH1, and OGG1 expression and TP53 mutation in diffuse-type adenocarcinoma of gastric cardia

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• 作者：Yukiko Kohno ; MD^a ; Hidetaka Yamamoto ; MD ; PhD^a ; Minako Hirahashi ; MD ; PhD^a ; Yoshiteru Kumagae ; MD^a ; Masafumi Nakamura ; MD ; PhD^b ; Eiji Oki ; MD ; PhD^c ; Yoshinao Oda ; MD ; PhD^a ; ^{oda@surgpath.med.kyushu-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Stomach ; Cardia ; Adenocarcinoma ; Oxidative stress ; Base excision repair enzymes
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：52
• 期：Complete
• 页码：145-152
• 全文大小：812 K

文摘

The effects of oxidative stress in adenocarcinomas of gastric cardia (AGCs) have not been fully elucidated. With a strict definition of AGC, we examined the immunohistochemical expressions of inducible nitric oxide synthase; 8-hydroxy-deoxyguanosine; and the base excision repair enzymes such as MUTYH, MTH1, and OGG1, and TP53 mutational status. Sixty-three cases of AGC were characterized by younger patient age (P = .0227) and more frequent venous invasion (P = .0106) compared with the adenocarcinomas of pylorus (APs). 8-hydroxy-deoxyguanosine was accumulated (P = .0011), whereas MUTYH (P = .0325) and OGG1 (P = .0007) were decreased, in the AGCs compared with the adjacent mucosa, but these differences were not detected in the APs. Among the AGCs, lower expressions of MUTYH (P = .0013) and MTH1 (P = .0059) were each significantly associated with diffuse-type histology. A lower expression of OGG1 was correlated with higher T-stage (P = .0011), lymphatic invasion (P = .004), and lymph node metastasis (P = .0094). In addition, the presence of TP53 mutation was associated with diffuse-type histology (P = .0153) and a lower level of MUTYH (P = .0221). The AGCs also showed a relatively high rate of a transversion-type mutation of TP53 (50%), whereas all TP53 mutations in the APs were transition type. Age 62 years or older (P = .0073), diffuse-type histology (P = .0020), and TP53 mutation (P = .0066) were each associated with worse survival in the AGC patients. Our results indicate that oxidative stress accumulation and a downregulation of base excision repair enzymes may play an important role in the pathogenesis of AGC, in particular diffuse-type AGCs. Diffuse-type AGC might involve molecular pathways different from those of other subsets of gastric cancer.