Mdm2 and p53 Expression in Radiation-Induced Sarcomas of the Head and Neck: Comparison with De Novo Sarcomas
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (23)
- Gonin-Laurent N, "Specific TP53 mutation pattern in radiation-induced sarcomas", Carcinogenesis, 27, pp.1266~1272 (2006)
- Gonin-Laurent N, "RB1 and TP53 pathways in radiation-induced sarcomas", Oncogene, 26, pp.6106~6112 (2007)
- Roch-Lefevre S, "Cytogenetic and molecular characterization of plutonium-induced rat osteosarcomas", J Radiat Res, 51, pp.243~250 (2010)
- Wu H, "Immunohistochemical analysis for Mdm2 and p53 proteins in methylcholanthrene-induced mouse rhabdomyosarcomas", J Vet Med Sci, 68, pp.427~431 (2006)
- Bjerkehagen B, "Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?", Br J Cancer, 106, pp.297~306 (2012)
- McHugh JB, "Primary versus radiation-associated craniofacial osteosarcoma: biologic and clinicopathologic comparisons", Cancer, 107, pp.554~562 (2006)
- Thijssens KM, "Radiation-induced sarcoma: a challenge for the surgeon", Ann Surg Oncol, 12, pp.237~245 (2005)
- Xi M, "Radiation-induced sarcoma in patients with nasopharyngeal carcinoma: a single-institution study", Cancer, 116, pp.5479~5486 (2010)
- Chan JY, "Postradiation sarcoma after radiotherapy for nasopharyngeal carcinoma", Laryngoscope, 122, pp.2695~2699 (2012)
- Barone G, "MDM2-p53 interaction in paediatric solid tumours: preclinical rationale, biomarkers and resistance", Curr Drug Targets, 15, pp.114~123 (2014)
- Ohnstad HO, "Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma", Cancer, 119, pp.1013~1022 (2013)
- Bjerkehagen B, "Radiation-induced sarcoma: 25-year experience from the Norwegian Radium Hospital", Acta Oncol, 47, pp.1475~1482 (2008)
- Murray EM, "Postradiation sarcomas: 20 cases and a literature review", Int J Radiat Oncol Biol Phys, 45, pp.951~961 (1999)
- Hadj-Hamou NS, "A transcriptome signature distinguished sporadic from postradiotherapy radiation-induced sarcomas", Carcinogenesis, 32, pp.929~934 (2011)
- Rumenapp C, "Secondary radiation-induced bone tumours demonstrate a high degree of genomic instability predictive of a poor prognosis", Curr Genomics, 13, pp.433~437 (2012)
- Canner JA, "MI-63: a novel small-molecule inhibitor targets MDM2 and induces apoptosis in embryonal and alveolar rhabdomyosarcoma cells with wild-type p53", Br J Cancer, 101, pp.774~781 (2009)
- Hameed M, "Pathology and genetics of adipocytic tumors", Cytogenet Genome Res, 118, pp.138~147 (2007)
- Sabah M, "Immunoreactivity of p53, Mdm2, p21(WAF1", CIP1) Bcl-2, and Bax in soft tissue sarcomas: correlation with histologic grade, 2007, pp.15, 64~69
- Wei Z, "Radiation-induced sarcoma in the head and neck region: a clinicopathologic and immunohistochemical study of 13 cases", Asian Pac J Cancer Prev, 12, pp.2995~2999 (2011)
- Wei Z, "Radiation-induced sarcoma of head and neck: 50 years of experience at a single institution in an endemic area of nasopharyngeal carcinoma in China", Med Oncol, 29, pp.670~676 (2012)
- Coindre JM, "Most malignant fibrous histiocytomas developed in the retroperitoneum are dedifferentiated liposarcomas: a review of 25 cases initially diagnosed as malignant fibrous histiocytoma", Mod Pathol, 16, pp.256~262 (2003)
- Le Guellec S, "Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?", Am J Surg Pathol, 38, pp.293~304 (2014)
- Binh MB, "MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data", Am J Surg Pathol, 29, pp.1340~1347 (2005)