Korean J Pathol.  2014 Oct;48(5):346-350. 10.4132/KoreanJPathol.2014.48.5.346.

Mdm2 and p53 Expression in Radiation-Induced Sarcomas of the Head and Neck: Comparison with De Novo Sarcomas

Affiliations
  • 1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. kjc@amc.seoul.kr
  • 2Department of Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 3Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 4Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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.

Keyword

Cancer, radiation induced; Head and neck neoplasms; Sarcoma; Mdm2 protein, human; Tumor suppressor protein p53
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