PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma.
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.
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Hyo Song
HS
Kim
Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea.
Seung Eun
SE
Lee
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Yoon Sung
YS
Bae
Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.
Dae Joon
DJ
Kim
Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
Chang Geol
CG
Lee
Department of Radiology, Yonsei University College of Medicine, Seoul, Korea.
Jin
J
Hur
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Hyunsoo
H
Chung
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Jun Chul
JC
Park
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Sung Kwan
SK
Shin
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Sang Kil
SK
Lee
Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Yong Chan
YC
Lee
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Hye Ryun
HR
Kim
Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young Mog
YM
Shim
Abbott Molecular Laboratories, Des Plaines, IL, United States.
Susan S
SS
Jewell
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Hyunki
H
Kim
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yoon La
YL
Choi
Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Byoung Chul
BC
Cho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D000077277:Esophageal Squamous Cell Carcinoma; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D015513:Oncogene Proteins / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models
D014408:Biomarkers, Tumor; D015513:Oncogene Proteins; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
PIK3CA; amplification; esophageal squamous cell carcinoma; fluorescent in situ hybridization; mutation