Prognostic and clinical impact of PIK3CA mutation in gastric cancer: pyrosequencing technology and literature review.

Kazuto Harada,Keisuke Miyake,Yoshifumi Baba,Kenichi Nakamura,Ryuma Tokunaga,Hideo Baba,Yasuo Sakamoto,Yuji Miyamoto,Daisuke Izumi,Hironobu Shigaki,Takatsugu Ishimoto,Naoya Yoshida,Yuki Kiyozumi,Masaaki Iwatsuki,Keisuke Kosumi,Masayuki Watanabe,Mayuko Ohuchi,Junji Kurashige

doi:10.1186/s12885-016-2422-y

Kazuto Harada, Keisuke Miyake + Show 16 more

Open Access

https://doi.org/10.1186/s12885-016-2422-y

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Abstract

BackgroundPhosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations that activate the PI3K/AKT signaling pathway have been observed in several types of carcinoma and have been associated with patient prognosis. However, the significance of PIK3CA mutations in gastric cancer remains unclear. This retrospective study investigated the relationship between PIK3CA mutations and clinical outcomes in patients with gastric cancer. Additionally, we reviewed the rate of PIK3CA mutations in gastric cancer and the association between PIK3CA mutations and prognosis in human cancers.MethodsThe study included 208 patients with gastric cancer who underwent surgical resection at Kumamoto University Hospital, Japan, between January 2001 and August 2010. Mutations in PIK3CA exons 9 and 20 were quantified by pyrosequencing assays.ResultsPIK3CA mutations were detected in 25 (12 %) of the 208 patients. Ten patients had c.1634A > G (p.E545G), 10 had c.1624G > A (p.E542K), 13 had c.1633G > A (p.E545K), nine had c.3139C > T (p.H1047R), and 1 had c.3140A > G (p.H1047Y) mutations. PIK3CA mutations were not significantly associated with any clinical, epidemiologic, or pathologic characteristic. Kaplan–Meier analysis showed no significant differences in disease-free survival (log rank P = 0.84) and overall survival (log rank P = 0.74) between patients with and without PIK3CA mutations.ConclusionsMutations in PIK3CA did not correlate with prognosis in patients with gastric cancer, providing additional evidence for the lack of relationship between the two.

Highlights

Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations that activate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway have been observed in several types of carcinoma and have been associated with patient prognosis
Elucidating the biological pathways leading to the development of gastric carcinoma is crucial because accumulation of genetic alterations has been shown to result in tumor development [2]
PIK3CA mutations and patient characteristics PIK3CA mutations were not significantly associated with any clinical, epidemiologic, or pathologic characteristic (Table 1)

Summary

Introduction

Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations that activate the PI3K/AKT signaling pathway have been observed in several types of carcinoma and have been associated with patient prognosis. The significance of PIK3CA mutations in gastric cancer remains unclear This retrospective study investigated the relationship between PIK3CA mutations and clinical outcomes in patients with gastric cancer. Elucidating the biological pathways leading to the development of gastric carcinoma is crucial because accumulation of genetic alterations has been shown to result in tumor development [2]. Mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, which encodes the p110 catalytic subunit of PI3K, have been found in several types of carcinoma [11, 12]. The hot spots of PIK3CA mutations have been located at five sites in exons 9 and 20 [13]

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