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

Yukiko Kohno, Hidetaka Yamamoto, Minako Hirahashi, Yoshiteru Kumagae, Masafumi Nakamura, Eiji Oki, Yoshinao Oda

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalHuman Pathology
Volume52
DOIs
Publication statusPublished - Jun 1 2016

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Cardia
Stomach
Adenocarcinoma
Mutation
Pylorus
Histology
Deoxyguanosine
DNA Repair
Oxidative Stress
Nitric Oxide Synthase Type II
Enzymes
Stomach Neoplasms
Mucous Membrane

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Reduced MUTYH, MTH1, and OGG1 expression and TP53 mutation in diffuse-type adenocarcinoma of gastric cardia. / Kohno, Yukiko; Yamamoto, Hidetaka; Hirahashi, Minako; Kumagae, Yoshiteru; Nakamura, Masafumi; Oki, Eiji; Oda, Yoshinao.

In: Human Pathology, Vol. 52, 01.06.2016, p. 145-152.

Research output: Contribution to journalArticle

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AU - Oki, Eiji

AU - Oda, Yoshinao

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