PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma

Content Provider	Semantic Scholar
Author	Kim, Hj. Lee, Seung Eun Bae, Yoon Sung Kim, Dae Joon Lee, Chang Geol Hur, Jin Ho Chung, Hyun Soo Park, Jun Chul Shin, Sung Kwan Lee, Sang Kil Lee, Yong Chan Kim, Hye Ryun Shim, Young Mog Jewell, Susan S. Kim, Hyunki Choi, Yoon-La Cho, Byoung Chul
Copyright Year	2016
Abstract	To investigate the clinicopathologic characteristics and the prognostic impact of PIK3CA gene amplification in curatively resected esophageal squamous cell carcinoma (ESCC). Using 534 curatively resected ESCCs, the PIK3CA gene copy number was evaluated with fluorescent in situ hybridization. PIK3CA amplification was defined as PIK3CA/centromere 3 ratio is ≥ 2.0 or average number of PIK3CA signals/tumor cell nucleus ≥ 5.0. PIK3CA mutations in exon 9 and 20, encoding the highly conserved helical and kinase domains were assessed by direct sequencing in 388 cases. PIK3CA amplification was detected in 56 (10.5%) cases. PIK3CA amplification was significantly associated with higher T-stage (P=0.026) and pathologic stage (P=0.053). PIK3CA amplification showed a significantly shorter disease free survival (DFS) compared with that of non-amplified group (33.4 vs 63.1 months, P=0.019). After adjusting for gender, tumor location, pathologic stage, histologic grade and adjuvant treatment, PIK3CA amplification was significantly associated with a shorter DFS (adjusted hazard ratio [AHR] 1.53; 95% CI, 1.10-2.17; P=0.02). Though the statistical insignificance, PIK3CA amplification showed tendency of shorter OS (52.1 vs 96.5 moths, P=0.116). PIK3CA mutations were detected in 6 (1.5%) of 388 cases; 5 cases with exon 9 mutations in E545K while one exon 20 mutation in H1047L. PIK3CA amplification is a frequent oncogenic alteration and associated with shorter survival, suggesting its role as a prognostic biomarker in resected ESCC. PIK3CA amplification may represent a promising therapeutic target for ESCC.
Starting Page	30691
Ending Page	30701
Page Count	11
File Format	PDF HTM / HTML
PubMed reference number	27095573v1
Alternate Webpage(s)	https://doi.org/10.18632/oncotarget.8749
DOI	10.18632/oncotarget.8749
Journal	Oncotarget
Volume Number	7
Language	English
Access Restriction	Open
Subject Keyword	Cell Nucleus Centromere Copy Number Direct Sequencing Disease-Free Survival Fluorescent in Situ Hybridization Forecast of outcome Gene Amplification Technique Hazard Ratio Histopathologic Grade Keratinized squamous cell of esophagus Mutation Neoplasms Neoplastic Cell Nucleic Acid Hybridization PIK3CA gene Patients Pharmaceutical Adjuvants Squamous Epithelial Cells Squamous cell carcinoma of esophagus
Content Type	Text
Resource Type	Article