Oncotarget

Research Papers:

Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers

Wen-Liang Fang, Kuo-Hung Huang, Yuan-Tzu Lan, Chien-Hsing Lin, Shih- Ching Chang _, Ming-Huang Chen, Yee Chao, Wen-Chang Lin, Su-Shun Lo, Anna Fen-Yau Li, Chew-Wun Wu, Shih-Hwa Chiou and Yi-Ming Shyr

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Oncotarget. 2016; 7:6201-6220. https://doi.org/10.18632/oncotarget.6641

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Abstract

Wen-Liang Fang1,2, Kuo-Hung Huang1,2,3, Yuan-Tzu Lan2,4, Chien-Hsing Lin5, Shih-Ching Chang2,4,*, Ming-Huang Chen2,6, Yee Chao2,6, Wen-Chang Lin7,8, Su-Shun Lo2,9, Anna Fen-Yau Li2,10, Chew-Wun Wu1,2, Shih-Hwa Chiou3,11,12, Yi-Ming Shyr1,2,*

1Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

2School of Medicine, National Yang-Ming University, Taipei City, Taiwan

3Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan

4Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

5Genome Research Center, National Yang-Ming University, Taipei City, Taiwan

6Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

7Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

8Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan

9National Yang-Ming University Hospital, Yilan City, Taiwan

10Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan

11Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei City, Taiwan

12Institute of Pharmacology, National Yang-Ming University, Taipei City, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Shih-Ching Chang, e-mail: changsc@vghtpe.gov.tw

Yi-Ming Shyr, e-mail: ymshyr@vghtpe.gov.tw

Keywords: PI3K/AKT pathway, PIK3CA amplifications, recurrence pattern, diffuse-type, prognosis

Received: August 08, 2015     Accepted: December 05, 2015     Published: December 17, 2015

ABSTRACT

Mutations in genes involved in the PI3K/AKT pathway and amplifications of the PIK3CA gene in gastric cancer and their associations with clinicopathological characteristics and EBV infection were analyzed in this study. A total of 431 patients with gastric adenocarcinomas were enrolled, and 39 mutation hotspots were evaluated in these patients using MALDI-TOF mass spectrometry were analyzed. PIK3CA amplifications were analyzed using real-time quantitative PCR. Regarding patients with intestinal-type gastric cancer, those with mutations in PI3K/AKT pathway genes were also more likely to have tumors located in the lower-third of the stomach than were those without mutations. Regarding patients with diffuse-type gastric cancer, those with PI3K/AKT pathway mutations were more likely to have tumors located in the upper-third of the stomach and to have more hematogenous metastases, particularly in the liver and lungs, than were patients without such mutations (22.2% vs. 4.5%). No significant survival difference was observed between patients with vs. without PI3K/AKT pathway mutations. Mutations in PI3K/AKT pathway genes were associated with hematogenous metastasis in patients with diffuse-type gastric cancer. Only when the tumors were located in the middle-third of stomach, tumor with mutations of the PIK3CA gene or mutations of the PI3K/AKT pathway genes were associated with more EBV infection than those without mutations. Patients with PIK3CA amplifications were more likely to have diffuse-type and poorly differentiated gastric cancers and were more likely to experience peritoneal recurrence compared with those without PIK3CA amplifications. Even upon subgroup analysis, PI3KCA amplifications were found to not affect the patients’ outcomes.


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