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

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...

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Detalles Bibliográficos
Autores principales: Song, Min Jeong, Song, Joon Seon, Roh, Jong-Lyel, Choi, Seung-Ho, Nam, Soon Yuhl, Kim, Sang Yoon, Kim, Sung Bae, Lee, Sang-wook, Cho, Kyung-Ja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Pathologists and The Korean Society for Cytopathology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215959/
https://www.ncbi.nlm.nih.gov/pubmed/25366069
http://dx.doi.org/10.4132/KoreanJPathol.2014.48.5.346
Descripción
Sumario: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.