title: p53 Mutation and MDM2 amplification in inflammatory myofibroblastic tumours.
abstract: OBJECTIVE
  The pathogenic mechanism and predictive indicators of biological behaviour of inflammatory myofibroblastic tumour are poorly understood. We investigated molecular abnormalities of p53 and MDM2 in order to assess whether these play an important role in pathogenesis, and whether they also contribute to clinicopathological aggressive phenotype in inflammatory myofibroblastic tumour.
  
  
  RESULTS
  We compared the immunohistochemical expression of calponin, h-caldesmon, ALK, and p53 gene mutation and MDM2 gene amplification with clinicopathological findings in 15 cases of inflammatory myofibroblastic tumour. Histologically, cellular atypia was observed in five (33.3%) out of 15 cases. Local recurrences were observed in two (14.3%) of 14 informative cases, but no distant metastasis was observed. The expression of calponin (9/14; 64%) but not h-caldesmon (0/14; 0%) was seen, which suggested myofibroblastic differentiation. ALK expression was seen in eight (53.3%) out of 15 cases, particularly in patients under 40 years old. Nuclear expression of p53 protein was recognized in only one (6.7%) of 15 cases, and polymerase chain reaction single-strand conformation polymorphism followed by direct sequencing revealed p53 gene missense mutations in two (13.3%) of 15 cases. Nuclear expression of MDM2 was seen in four (26.7%) of 15 cases, and the MDM2 gene amplification was observed in two of the four cases.
  
  
  CONCLUSIONS
  Inflammatory myofibroblastic tumour shows a wide spectrum of cellular atypia and biological behaviour with p53 and MDM2 expression. However, the alterations in the p53 pathway seem not to play a major role in the pathogenesis of inflammatory myofibroblastic tumour.
authors.affiliation: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: A
authors.initials: A
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Miyajima
authors.forename: S
authors.initials: S
authors.lastname: Tamiya
authors.forename: M
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D016158:Genes, p53; D006104:Granuloma, Plasma Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D009379:Neoplasms, Muscle Tissue / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D020794:Receptor Protein-Tyrosine Kinases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D000096985:Calponins
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D020794:Receptor Protein-Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D000096985:Calponins; C497206:MDM2 protein, human; C000626173:ALK protein, human