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PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma.
Oncotarget. 2016 May 24; 7(21):30691-701.O

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.

Authors+Show Affiliations

Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea.Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.Department of Radiology, Yonsei University College of Medicine, Seoul, Korea.Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Abbott Molecular Laboratories, Des Plaines, IL, United States.Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27095573

Citation

Kim, Hyo Song, et al. "PIK3CA Amplification Is Associated With Poor Prognosis Among Patients With Curatively Resected Esophageal Squamous Cell Carcinoma." Oncotarget, vol. 7, no. 21, 2016, pp. 30691-701.
Kim HS, Lee SE, Bae YS, et al. PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Oncotarget. 2016;7(21):30691-701.
Kim, H. S., Lee, S. E., Bae, Y. S., Kim, D. J., Lee, C. G., Hur, J., Chung, H., Park, J. C., Shin, S. K., Lee, S. K., Lee, Y. C., Kim, H. R., Shim, Y. M., Jewell, S. S., Kim, H., Choi, Y. L., & Cho, B. C. (2016). PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Oncotarget, 7(21), 30691-701. https://doi.org/10.18632/oncotarget.8749
Kim HS, et al. PIK3CA Amplification Is Associated With Poor Prognosis Among Patients With Curatively Resected Esophageal Squamous Cell Carcinoma. Oncotarget. 2016 May 24;7(21):30691-701. PubMed PMID: 27095573.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. AU - Kim,Hyo Song, AU - Lee,Seung Eun, AU - Bae,Yoon Sung, AU - Kim,Dae Joon, AU - Lee,Chang Geol, AU - Hur,Jin, AU - Chung,Hyunsoo, AU - Park,Jun Chul, AU - Shin,Sung Kwan, AU - Lee,Sang Kil, AU - Lee,Yong Chan, AU - Kim,Hye Ryun, AU - Shim,Young Mog, AU - Jewell,Susan S, AU - Kim,Hyunki, AU - Choi,Yoon La, AU - Cho,Byoung Chul, PY - 2015/09/24/received PY - 2016/03/31/accepted PY - 2016/4/21/entrez PY - 2016/4/21/pubmed PY - 2017/12/30/medline KW - PIK3CA KW - amplification KW - esophageal squamous cell carcinoma KW - fluorescent in situ hybridization KW - mutation SP - 30691 EP - 701 JF - Oncotarget JO - Oncotarget VL - 7 IS - 21 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27095573/PIK3CA_amplification_is_associated_with_poor_prognosis_among_patients_with_curatively_resected_esophageal_squamous_cell_carcinoma_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=8749 DB - PRIME DP - Unbound Medicine ER -