title: Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma.
abstract: BACKGROUND
  The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target.
  
  
  METHODS
  We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10).
  
  
  RESULTS
  Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro.
  
  
  CONCLUSIONS
  FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;; 2. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ito
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Akira
authors.initials: A
authors.lastname: Maekawa
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kuda
authors.affiliation: 3. Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Hoshina
authors.affiliation: 3. Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Riichiro
authors.initials: R
authors.lastname: Abe
authors.affiliation: 2. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.affiliation: 1. Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
keywords: Forkhead box M1; Kaposi's sarcoma; angiosarcoma; docetaxel; prognosis; siRNA; thiostrepton.; treatment