Prognostic implications ofPIK3CAamplification in curatively resected liposarcoma

// Joo Hoon Kim 1, * , Jae Seok Lee 2, * , Eo Jin Kim 2 , Kyu Hyun Park 3 , Ki Hyang Kim 4 , Seong Yoon Yi 5 , Han Seong Kim 6 , Yong Jin Cho 7 , Kyoo-Ho Shin 7 , Joong Bae Ahn 1 , Hyuk Hu 8 , Kyung Sik Kim 8 , Young Deuk Choi 9 , Sunghoon Kim 10 , Young Han Lee 11 , Jin-Suck Suh 11 , Sung Hoon Noh 8 , Sun Young Rha 1 , Hyo Song Kim 1 1 Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea 2 Department of Pathology, Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang, Korea 3 Cancer Metastasis Research Center, Song Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea 4 Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea 5 Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea 6 Department of Pathology, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea 7 Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, Korea 8 Department of Surgery, Yonsei University College of Medicine, Seoul, Korea 9 Department of Urology, Yonsei University College of Medicine, Seoul, Korea 10 Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea 11 Department of Radiology, Yonsei University College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Sun Young Rha, e-mail: rha7655@yuhs.ac Hyo Song Kim, e-mail: hyosong77@yuhs.ac Keywords: liposarcoma, PIK3CA, amplification, mutation Received: January 05, 2016 Accepted: March 02, 2016 Published: March 21, 2016 ABSTRACT 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.