title: High IGF2 and FGFR3 are associated with tumour progression in undifferentiated pleomorphic sarcomas, but EGFR and FGFR3 mutations are a rare event.
abstract: OBJECTIVE
  Pleomorphic undifferentiated sarcomas (formerly known as malignant fibrous histiocytomas) are recognised by the actual WHO classification as an undifferentiated, unclassifiable category of pleomorphic sarcomas which show no definable line of differentiation and are still a diagnosis of exclusion. Therefore, diagnostic, prognostic and therapeutic options of these tumours are urgently needed.
  
  
  METHODS
  Three hundred and twenty-seven spindle cell tumours of a German consultation and reference centre of soft tissue tumours consisting of 200 undifferentiated pleomorphic sarcomas (UPS), 45 low-grade sarcomas (10 low-grade fibromyxoid sarcomas, 32 low-grade myofibroblastic sarcomas and three myxoinflammatory fibroblastic sarcomas) and 82 tumours of the fasciitis family were revisited. The specimens were analysed immunohistochemically with distinct markers including tyrosine kinases and expression correlated with clinicopathological parameters. Additionally, mutational analysis was performed on specimens with high expression of EGFR and FGFR3.
  
  
  RESULTS
  At the protein level high IGF2 expression was observed in 86 %, FGFR3 (69 %), PDGFRA (62 %), PDGFRB (39 %), FGFR1 (8 %), EGFR (5 %), KDR/VEGFR2 (3 %), ALK (0 %) and high Ki67 (63 %) in UPS. High expressions of IGF2 and FGFR3 are significantly correlated with a higher grading (p = 0.023 and p = 0.016, respectively) and a high Ki67 index (p = 0.017 and p = 0.001, respectively). No mutations were found in the hot spots of tumour specimens with a high expression of EGFR gene (exons 18-21) and FGFR3 gene (exons 7, 10 and 15).
  
  
  CONCLUSIONS
  High expressions of IGF2 and FGFR3 are significantly associated with tumour progression, grading and Ki67 and might classify a subgroup of undifferentiated pleomorphic sarcoma. These markers might guide targeted therapies in these neoplasms.
authors.affiliation: Institute of Pathology, Friedrich-Schiller University, Jena, Germany.
authors.forename: Katinka
authors.initials: K
authors.lastname: Rüping
authors.forename: Annelore
authors.initials: A
authors.lastname: Altendorf-Hofmann
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Eric
authors.initials: E
authors.lastname: Kampmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gibis
authors.forename: Lars
authors.initials: L
authors.lastname: Lindner
authors.forename: Detlef
authors.initials: D
authors.lastname: Katenkamp
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II; C512478:EGFR protein, human; D066246:ErbB Receptors; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3