Prognostic implications of PIK3CA amplification in curatively resected liposarcoma
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Joo Hoon Kim1,*, Jae Seok Lee2,*, Eo Jin Kim2, Kyu Hyun Park3, Ki Hyang Kim4, Seong Yoon Yi5, Han Seong Kim6, Yong Jin Cho7, Kyoo-Ho Shin7, Joong Bae Ahn1, Hyuk Hu8, Kyung Sik Kim8, Young Deuk Choi9, Sunghoon Kim10, Young Han Lee11, Jin-Suck Suh11, Sung Hoon Noh8, Sun Young Rha1, Hyo Song Kim1
1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
2Department of Pathology, Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang, Korea
3Cancer Metastasis Research Center, Song Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea
4Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
5Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea
6Department of Pathology, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea
7Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea
8Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
9Department of Urology, Yonsei University College of Medicine, Seoul, Korea
10Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea
11Department of Radiology, Yonsei University College of Medicine, Seoul, Korea
*These authors have contributed equally to this work
Sun Young Rha, e-mail: email@example.com
Hyo Song Kim, e-mail: firstname.lastname@example.org
Keywords: liposarcoma, PIK3CA, amplification, mutation
Received: January 05, 2016 Accepted: March 02, 2016 Published: March 21, 2016
Background: We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma.
Patients and methods: A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH).
Results: Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival.
Conclusions: We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.
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