Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas

Razia,Sultana; Nakayama,Kentaro; Nakamura,Kohei; Ishibashi,Tomoka; Ishikawa,Masako; Minamoto,Toshiko; Iida,Kouji; Otsuki,Yoshiro; Nakayama,Satoru; Ishikawa,Noriyoshi; Kyo,Satoru

doi:10.3892/etm.2019.7771

Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas

Authors:
- Sultana Razia
- Kentaro Nakayama
- Kohei Nakamura
- Tomoka Ishibashi
- Masako Ishikawa
- Toshiko Minamoto
- Kouji Iida
- Yoshiro Otsuki
- Satoru Nakayama
- Noriyoshi Ishikawa
- Satoru Kyo
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Affiliations: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Shimane 693‑8501, Japan, Department of Pathology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka 430‑8558, Japan, Department of Obstetrics and Gynecology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka 430‑8558, Japan, Department of Organ Pathology, Shimane University School of Medicine, Izumo, Shimane 693‑8501, Japan
Published online on: July 12, 2019 https://doi.org/10.3892/etm.2019.7771
Pages: 2278-2284

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Abstract

The aim of the present study was to evaluate the mutation and amplification status of the phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α (PIK3CA) gene, as well as the association with clinicopathological characteristics and prognosis, in Japanese patients with cervical cancer. Fluorescence in situ hybridization and polymerase chain reaction were performed to assess PIK3CA gene amplification and mutation. The inhibitors temsirolimus and NVP‑BEZ235 were used to inactivate the phosphatidylinositide 3‑kinase (PI3K)/AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin kinase (mTOR) pathway to clarify the roles of PI3K/AKT activation in cervical carcinoma cells harboring associated mutations. Four somatic point mutations (4/71, 5.6%) were found in exon 20 in cervical squamous cell carcinoma samples, whereas three (3/53, 5.7%) were found in exon 9 in cervical adeno/adenosquamous cell carcinoma samples. Amplification of PIK3CA was also observed in this study and amplification was more commonly found in adeno/adenosquamous carcinomas than in cervical squamous cell carcinomas (20.7 vs. 1.4%, respectively, P=0.0003). No significant correlation was obesrved between PIK3CA amplification and progression free survival (P=0.7576) or overall survival (P=0.8859). Moreover, no association between PIK3CA mutation and sensitivity to PI3K/AKT/mTOR inhibitors was observed in cervical carcinoma cells. These results suggest that in Japanese patients with cervical cancer, PIK3CA mutation and amplification cannot act as biomarkers for individualized molecular targeted therapy.

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