PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma
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Hyo Song Kim1,*, Seung Eun Lee2,*, Yoon Sung Bae3,*, Dae Joon Kim4, Chang Geol Lee5, Jin Hur6, Hyunsoo Chung7, Jun Chul Park7, Sung Kwan Shin7, Sang Kil Lee7, Yong Chan Lee7, Hye Ryun Kim1, Young Mog Shim8, Susan S. Jewell9, Hyunki Kim3, Yoon-La Choi10, Byoung Chul Cho1
1Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
2Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea
3Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
4Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea
5Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea
6Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
7Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
8Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
9Abbott Molecular Laboratories, Des Plaines, IL, United States
10Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
*These authors have contributed equally to this work as co-first authors
Byoung Chul Cho, email: [email protected]
Yoon-La Choi, email: [email protected]
Hyunki Kim, email: [email protected]
Keywords: PIK3CA, esophageal squamous cell carcinoma, amplification, mutation, fluorescent in situ hybridization
Received: September 24, 2015 Accepted: March 31, 2016 Published: April 15, 2016
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.
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