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

Song MJ, Song JS, Roh JL, Choi SH, Nam SY, Kim SY, Kim SB, Lee SW, Cho KJ - Korean J Pathol (2014)

Bottom Line: Variable immunoprofiles observed in both groups did not correlate with tumor types, except that all of 2 myxofibrosarcomas were Mdm2(+)/p53(+).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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology, 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.

No MeSH data available.


Related in: MedlinePlus

Mdm2 (B, E, H, K) and p53 (C, F, I, L) expression in sarcomas. (A–C) Mdm2-positive, p53-negative de novo osteosarcoma. (D–F) Mdm2-positive, p53-positive de novo myxofibrosarcoma. (G–I) Mdm2-negative, p53-positive radiation-induced osteosarcoma. (J–L) Mdm2-negative, p53-negative radiation-induced fibrosarcoma.
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f1-kjpathol-48-5-346: Mdm2 (B, E, H, K) and p53 (C, F, I, L) expression in sarcomas. (A–C) Mdm2-positive, p53-negative de novo osteosarcoma. (D–F) Mdm2-positive, p53-positive de novo myxofibrosarcoma. (G–I) Mdm2-negative, p53-positive radiation-induced osteosarcoma. (J–L) Mdm2-negative, p53-negative radiation-induced fibrosarcoma.

Mentions: Mdm2 expression was less common in RIS (3/8, 37.5%) than in de novo cases (6/8, 75%) (p<.05), while p53 expression was more common in RIS cases (75% vs 37.5%) (p<.05). Variable combination types of expression were observed in both groups (Table 2, Fig. 1); however, while half of RISs were Mdm2(–)/p53(+), none of de novo cases showed such combination, and while half of de novo sarcomas were Mdm2(+)/p53(–), which can be the candidate group of Mdm2 inhibitors, only 1 RIS showed such a combination. The expression profiles of Mdm2 and p53 did not correlate with tumor types, except that both of the myxofibrosarcomas, 1 RIS case and 1 de novo case, were positive for both Mdm2 and p53 (Table 2, Fig. 1).


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

Song MJ, Song JS, Roh JL, Choi SH, Nam SY, Kim SY, Kim SB, Lee SW, Cho KJ - Korean J Pathol (2014)

Mdm2 (B, E, H, K) and p53 (C, F, I, L) expression in sarcomas. (A–C) Mdm2-positive, p53-negative de novo osteosarcoma. (D–F) Mdm2-positive, p53-positive de novo myxofibrosarcoma. (G–I) Mdm2-negative, p53-positive radiation-induced osteosarcoma. (J–L) Mdm2-negative, p53-negative radiation-induced fibrosarcoma.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215959&req=5

f1-kjpathol-48-5-346: Mdm2 (B, E, H, K) and p53 (C, F, I, L) expression in sarcomas. (A–C) Mdm2-positive, p53-negative de novo osteosarcoma. (D–F) Mdm2-positive, p53-positive de novo myxofibrosarcoma. (G–I) Mdm2-negative, p53-positive radiation-induced osteosarcoma. (J–L) Mdm2-negative, p53-negative radiation-induced fibrosarcoma.
Mentions: Mdm2 expression was less common in RIS (3/8, 37.5%) than in de novo cases (6/8, 75%) (p<.05), while p53 expression was more common in RIS cases (75% vs 37.5%) (p<.05). Variable combination types of expression were observed in both groups (Table 2, Fig. 1); however, while half of RISs were Mdm2(–)/p53(+), none of de novo cases showed such combination, and while half of de novo sarcomas were Mdm2(+)/p53(–), which can be the candidate group of Mdm2 inhibitors, only 1 RIS showed such a combination. The expression profiles of Mdm2 and p53 did not correlate with tumor types, except that both of the myxofibrosarcomas, 1 RIS case and 1 de novo case, were positive for both Mdm2 and p53 (Table 2, Fig. 1).

Bottom Line: Variable immunoprofiles observed in both groups did not correlate with tumor types, except that all of 2 myxofibrosarcomas were Mdm2(+)/p53(+).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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Pathology, 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.

No MeSH data available.


Related in: MedlinePlus