title: Mdm2 and p53 Expression in Radiation-Induced Sarcomas of the Head and Neck: Comparison with De Novo Sarcomas.
abstract: BACKGROUND
  The pathogenesis of radiation-induced sarcomas (RISs) is not well known. In RIS, TP53 mutations are frequent, but little is known about Mdm2-p53 interaction, which is a recent therapeutic target of sarcomas.
  
  
  METHODS
  We studied the immunohistochemical expression of Mdm2 and p53 of 8 RISs. The intervals between radiation therapy and diagnosis of secondary sarcomas ranged from 3 to 17 years.
  
  
  RESULTS
  Mdm2 expression was more common in de novo sarcomas than RISs (75% vs 37.5%), and p53 expression was more common in RISs than in de novo cases (75% vs 37.5%). While half of the RISs were Mdm2(-)/p53(+), none of de novo cases showed such combination; while half of de novo sarcomas were Mdm2(+)/p53(-), which are a candidate group of Mdm2 inhibitors, only 1 RIS showed such a combination. Variable immunoprofiles observed in both groups did not correlate with tumor types, except that all of 2 myxofibrosarcomas were Mdm2(+)/p53(+).
  
  
  CONCLUSIONS
  In conclusion, we speculated that both radiation-induced and de novo sarcomagenesis are not due to a unique genetic mechanism. Mdm2-expression without p53 overexpression in 1 case of RIS decreases the future possibility of applying Mdm2 inhibitors on a subset of these difficult tumors.
authors.affiliation: Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Song
authors.affiliation: Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Joon Seon
authors.initials: JS
authors.lastname: Song
authors.affiliation: Departments of Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jong-Lyel
authors.initials: JL
authors.lastname: Roh
authors.affiliation: Departments of Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Departments of Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Soon Yuhl
authors.initials: SY
authors.lastname: Nam
authors.affiliation: Departments of Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Departments of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sung Bae
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Departments of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyung-Ja
authors.initials: KJ
authors.lastname: Cho
keywords: Cancer, radiation induced; Head and neck neoplasms; Mdm2 protein, human; Sarcoma; Tumor suppressor protein p53