title: Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of uncertain malignant potential.
abstract: OBJECTIVE
  It has been suggested that p16 is overexpressed in uterine leiomyosarcomas in comparison with leiomyomas. In this study, p16 immunohistochemical expression was assessed in a variety of uterine smooth muscle tumours, including usual leiomyomas, leiomyoma variants, smooth muscle tumours of uncertain malignant potential (STUMPs) and leiomyosarcomas. The aim was to ascertain whether there are differences in p16 expression between these groups and whether p16 is of potential value in the assessment of problematic uterine smooth muscle neoplasms. p16 expression was also compared with that of p53 and MIB1.
  
  
  RESULTS
  Cases of usual leiomyoma (n = 10), leiomyoma variants (n = 27), STUMP (n = 4) and leiomyosarcoma (n = 22) were subject to p16, p53 and MIB1 immunohistochemistry. For p16, cases were evaluated with respect to both staining distribution and intensity. There was a statistically significant difference in p16 distribution (P < 0.001) and intensity (P = 0.001) between leiomyosarcomas and the other groups. There was no difference in p16 expression between usual leiomyomas, leiomyoma variants and STUMPs. There were also statistically significant differences in p53 (P = 0.014) and MIB1 (P < 0.001) immunoreactivity between leiomyosarcomas and the other groups.
  
  
  CONCLUSIONS
  p16 is overexpressed in uterine leiomyosarcomas compared with leiomyomas, benign leiomyoma variants and STUMPs, suggesting that p16 may be implicated in the pathogenesis of malignant uterine smooth muscle neoplasms. p16, in combination with p53 and MIB1, may be of value as an adjunct to morphological examination in the assessment of problematic uterine smooth muscle tumours, although further large-scale studies with follow-up are necessary to confirm this.
authors.affiliation: Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: O'Neill
authors.forename: H A
authors.initials: HA
authors.lastname: McBride
authors.forename: L E
authors.initials: LE
authors.lastname: Connolly
authors.forename: W G
authors.initials: WG
authors.lastname: McCluggage
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002452:Cell Count; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D018235:Smooth Muscle Tumor / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases