Clinicopathological and biological analysis of
| Autor: | Sultana Razia, Masako Ishikawa, Noriyoshi Ishikawa, Satoru Nakayama, Toshiko Minamoto, Satoru Kyo, Kentaro Nakayama, Tomoka Ishibashi, Kohei Nakamura, Yoshiro Otsuki, Kouji Iida |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cervical cancer Cancer Research cervical cancer PIK3CA gene amplification gene mutation squamous cell carcinoma adeno adenosquamous cell carcinoma biology business.industry Point mutation Cancer General Medicine Articles Gene mutation medicine.disease PIK3CA Gene Amplification 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immunology and Microbiology (miscellaneous) 030220 oncology & carcinogenesis Cancer research medicine biology.protein business Protein kinase B Mechanistic target of rapamycin PI3K/AKT/mTOR pathway |
| Zdroj: | Experimental and therapeutic medicine. 18(3) |
| ISSN: | 1792-0981 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|