title: TOP2A copy number and TOP2A expression in uterine benign smooth muscle tumours and leiomyosarcoma.
abstract: OBJECTIVE
  To examine TOP2A copy number, TOP2A expression, and its prognostic value in uterine leiomyosarcoma (LMS) and other benign smooth muscle tumours.
  
  
  METHODS
  We analysed 37 patients treated for uterine LMS with immunohistochemistry for protein expression and fluorescence in situ hybridisation (FISH) for copy number. Twelve cases of leiomyoma variants (LMVs), 4 smooth muscle tumours of uncertain malignant potential (STUMP) and 23 leiomyomas (LMs) were also included.
  
  
  RESULTS
  Eighteen patients with LMS (48.6%) were International Federation of Gynecology and Obstetrics (FIGO) stage I, six (16.2%) were stage II, four (10.8%) were stage III, and nine (24.3%) were stage IV. Twenty-one (56.8%) patients with LMS showed high expression of TOP2A. Greater TOP2A levels were found in patients with stage ≥II disease compared with stage I and also in high mitotic index tumours (>20/10 HPF (high power field)). Eleven (36.7%) cases had abnormal TOP2A copy numbers. There was no link between TOP2A copy number and TOP2A expression. All patients with benign smooth muscle tumours had low TOP2A immunohistochemical expression and one (7.7%) patient had TOP2A amplification. TOP2A expression and TOP2A copy number had no impact on disease outcomes. Only the presence of disease outside of the uterus negatively impacted survival compared with early disease (53.4 vs 15.8 months; p<0.001).
  
  
  CONCLUSIONS
  TOP2A is highly expressed in advanced LMS but not in non-malignant diseases. TOP2A expression does not correlate with FISH results and does not predict outcome. TOP2A levels are higher in high-mitotic index tumours and in more advanced stages of disease.
authors.affiliation: Department of Gynecologic Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Glauco
authors.identifier: http://orcid.org/0000-0002-8193-5582
authors.initials: G
authors.lastname: Baiocchi
authors.affiliation: Department of Gynecologic Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Fernando Luís Visoni
authors.initials: FL
authors.lastname: Poliseli
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Louise
authors.initials: L
authors.lastname: De Brot
authors.affiliation: Department of Gynecologic Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Henrique
authors.initials: H
authors.lastname: Mantoan
authors.affiliation: Department of Gynecologic Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Beatriz Nunes
authors.initials: BN
authors.lastname: Schiavon
authors.affiliation: Department of Gynecologic Oncology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Carlos Chaves
authors.initials: CC
authors.lastname: Faloppa
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Jose
authors.initials: J
authors.lastname: Vassallo
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil.
authors.forename: Isabela Werneck
authors.initials: IW
authors.lastname: Cunha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007889:Leiomyoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D018235:Smooth Muscle Tumor / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D014599:Uterus / Q000378:metabolism / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human
keywords: FISH; IMMUNOHISTOCHEMISTRY; SARCOMAS; UTERUS