title: Genetic profiling identifies two classes of soft-tissue leiomyosarcomas with distinct clinical characteristics.
abstract: OBJECTIVE
  Data about the prognostic factors of soft-tissue leiomyosarcomas and their correlation with molecular profile are limited.
  
  
  METHODS
  From 1990 to 2010, 586 adult patients with a primary soft-tissue leiomyosarcoma were included in the French Sarcoma Group (GSF) database after surgery of the primary tumor. Multivariate analyses were conducted by Cox regression model in a backward stepwise procedure. Genetic profiling was conducted for 73 cases.
  
  
  RESULTS
  Median age was 59 years (range, 21-98 years). The median follow-up of patients alive was 46 months. The 5-year metastasis-free survival (MFS) rate was 51% (95% location and grade > I were independent adverse prognostic factors for MFS). The 5-year overall survival (OS) rate was 63% [95% confidence interval (CI), 59-67]. On multivariate analysis, age ≥ 60 years old, tumor size > 5 cm, deep location, and grade > I were independent adverse prognostic factors for OS. Molecular profiling identified specific clusters with activation of different biologic pathways: retroperitoneal leiomyosarcomas are characterized by overexpression of genes involved in muscle differentiation and nonretroperitoneal leiomyosarcomas characterized by overexpression of genes mainly involved in extracellular matrix, wounding, and adhesion pathways. The CINSARC signature but not comparative genomic hybridization (CGH) profiling was predictive of outcome.
  
  
  CONCLUSIONS
  Soft-tissue leiomyosarcomas represent a heterogeneous group of tumors with at least two categories, retroperitoneal and extremities leiomyosarcomas, having specific clinical outcome and molecular features. Future clinical trials should consider this heterogeneity for a better stratification of patients.
authors: Department of Medical Oncology, INSERM U916, Institut Bergonie, Bordeaux, France. a.italiano@bordeaux.unicancer.fr
authors: Antoine
authors: A
authors: Italiano
authors: Pauline
authors: P
authors: Lagarde
authors: Céline
authors: C
authors: Brulard
authors: Philippe
authors: P
authors: Terrier
authors: Marick
authors: M
authors: Laë
authors: Bernard
authors: B
authors: Marques
authors: Dominique
authors: D
authors: Ranchere-Vince
authors: Jean-Jacques
authors: JJ
authors: Michels
authors: Martine
authors: M
authors: Trassard
authors: Angela
authors: A
authors: Cioffi
authors: Sophie
authors: S
authors: Piperno-Neumann
authors: Christine
authors: C
authors: Chevreau
authors: Jean-Yves
authors: JY
authors: Blay
authors: Corinne
authors: C
authors: Delcambre
authors: Nicolas
authors: N
authors: Isambert
authors: Nicolas
authors: N
authors: Penel
authors: Jacques-Olivier
authors: JO
authors: Bay
authors: Sylvie
authors: S
authors: Bonvalot
authors: Axel
authors: A
authors: Le Cesne
authors: Jean-Michel
authors: JM
authors: Coindre
authors: Frédéric
authors: F
authors: Chibon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D055028:Comparative Genomic Hybridization; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007890:Leiomyosarcoma / Q000145:classification* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012983:Soft Tissue Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor