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

Authors
 Hyo Song Kim  ;  Seung Eun Lee  ;  Yoon Sung Bae  ;  Dae Joon Kim  ;  Chang Geol Lee  ;  Jin Hur  ;  Hyunsoo Chung  ;  Jun Chul Park  ;  Sung Kwan Shin  ;  Sang Kil Lee  ;  Yong Chan Lee  ;  Hye Ryun Kim  ;  Young Mog Shim  ;  Susan S. Jewell  ;  Hyunki Kim  ;  Yoon-La Choi  ;  Byoung Chul Cho 
Citation
 Oncotarget, Vol.7(21) : 30691-30701, 2016 
Journal Title
 Oncotarget 
Issue Date
2016
MeSH
Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Carcinoma, Squamous Cell/genetics* ; Carcinoma, Squamous Cell/mortality* ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/surgery ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Disease-Free Survival ; Esophageal Neoplasms/genetics* ; Esophageal Neoplasms/mortality* ; Esophageal Neoplasms/pathology ; Esophageal Neoplasms/surgery ; Exons/genetics ; Female ; Follow-Up Studies ; Gene Amplification* ; Gene Dosage ; Humans ; In Situ Hybridization, Fluorescence ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Oncogene Proteins/genetics ; Prognosis ; Proportional Hazards Models
Keywords
PIK3CA ; amplification ; esophageal squamous cell carcinoma ; fluorescent in situ hybridization ; mutation
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.
Files in This Item:
T201602229.pdf Download
DOI
10.18632/oncotarget.8749
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dae Joon(김대준)
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Park, Jun Chul(박준철) ORCID logo https://orcid.org/0000-0001-8018-0010
Bae, Yoon Sung(배윤성)
Shin, Sung Kwan(신성관) ORCID logo https://orcid.org/0000-0001-5466-1400
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
Lee, Yong Chan(이용찬) ORCID logo https://orcid.org/0000-0001-8800-6906
Lee, Chang Geol(이창걸) ORCID logo https://orcid.org/0000-0002-8702-881X
Chung, Hyun Soo(정현수)
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Hur, Jin(허진) ORCID logo https://orcid.org/0000-0002-8651-6571
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147182
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