Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma

Yukiko Takahashi, Yoshinao Oda, Ken Ichi Kawaguchi, Sadafumi Tamiya, Hidetaka Yamamoto, Sachiyo Suita, Masazumi Tsuneyoshi

Research output: Contribution to journalArticle

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Abstract

Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in children. Some reports have discussed the altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma; however, variable frequencies of occurrence have been noted. In the current study, among 72 cases of rhabdomyosarcoma, the authors evaluated for the expression of p53, MDM2, p16, p21/WAF1, p27, cyclin D1, cyclin E, pRb and E2F-1 protein immunohistochemically and assessed for proliferative activities using MIB-1. We also analyzed the mutation of the p53 gene in 45 cases, the amplification of the MDM2 gene in 18 cases and the mutation of the H-ras gene in 29 cases, using formalin-fixed paraffin-embedded materials. Furthermore, we assessed the correlation between clinicopathologic factors and the results of both immunohistochemical and molecular analyses. Alveolar type affected older patients, and it had a significantly higher mitotic rate compared with the embryonal type (P = 0.0226). p53 overexpression was detected in 22 (30.6%) of 72 cases, and 10 (22.2%) of 45 cases had p53 gene abnormalities. As for MDM2, its overexpression was found in nine (12.5%) of 72 cases, and three (16.7%) of 18 cases showed MDM2 amplification. A statistically significant association was observed between immunoreaction for MDM2 and p53 overexpression (P = 0.0002), and p53 and MDM2 overexpression was significantly correlated with high MIB-1 labeling indices. E2F-1 labeling indices showed a significantly higher score in alveolar type compared with that seen in embryonal type (P = 0.0334), but MIB-1 did not. In conclusion, our study suggests that p53 overexpression may be related to tumor progression because tumors with p53 overexpression have a high proliferative activity in the current study. Alveolar type had a significantly higher both mitotic rate and E2F-1 labeling indices when compared with the embryonal type. The current study is the first report of the correlation of E2F-1 with alveolar rhabdomyosarcoma.

Original languageEnglish
Pages (from-to)660-669
Number of pages10
JournalModern Pathology
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 1 2004

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Cell Cycle Proteins
Rhabdomyosarcoma
p53 Genes
Alveolar Rhabdomyosarcoma
E2F Transcription Factors
Cyclin E
Mutation
ras Genes
Gene Amplification
Cyclin D1
Sarcoma
Paraffin
Formaldehyde
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma. / Takahashi, Yukiko; Oda, Yoshinao; Kawaguchi, Ken Ichi; Tamiya, Sadafumi; Yamamoto, Hidetaka; Suita, Sachiyo; Tsuneyoshi, Masazumi.

In: Modern Pathology, Vol. 17, No. 6, 01.06.2004, p. 660-669.

Research output: Contribution to journalArticle

Takahashi, Yukiko ; Oda, Yoshinao ; Kawaguchi, Ken Ichi ; Tamiya, Sadafumi ; Yamamoto, Hidetaka ; Suita, Sachiyo ; Tsuneyoshi, Masazumi. / Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma. In: Modern Pathology. 2004 ; Vol. 17, No. 6. pp. 660-669.
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abstract = "Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in children. Some reports have discussed the altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma; however, variable frequencies of occurrence have been noted. In the current study, among 72 cases of rhabdomyosarcoma, the authors evaluated for the expression of p53, MDM2, p16, p21/WAF1, p27, cyclin D1, cyclin E, pRb and E2F-1 protein immunohistochemically and assessed for proliferative activities using MIB-1. We also analyzed the mutation of the p53 gene in 45 cases, the amplification of the MDM2 gene in 18 cases and the mutation of the H-ras gene in 29 cases, using formalin-fixed paraffin-embedded materials. Furthermore, we assessed the correlation between clinicopathologic factors and the results of both immunohistochemical and molecular analyses. Alveolar type affected older patients, and it had a significantly higher mitotic rate compared with the embryonal type (P = 0.0226). p53 overexpression was detected in 22 (30.6{\%}) of 72 cases, and 10 (22.2{\%}) of 45 cases had p53 gene abnormalities. As for MDM2, its overexpression was found in nine (12.5{\%}) of 72 cases, and three (16.7{\%}) of 18 cases showed MDM2 amplification. A statistically significant association was observed between immunoreaction for MDM2 and p53 overexpression (P = 0.0002), and p53 and MDM2 overexpression was significantly correlated with high MIB-1 labeling indices. E2F-1 labeling indices showed a significantly higher score in alveolar type compared with that seen in embryonal type (P = 0.0334), but MIB-1 did not. In conclusion, our study suggests that p53 overexpression may be related to tumor progression because tumors with p53 overexpression have a high proliferative activity in the current study. Alveolar type had a significantly higher both mitotic rate and E2F-1 labeling indices when compared with the embryonal type. The current study is the first report of the correlation of E2F-1 with alveolar rhabdomyosarcoma.",
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AU - Yamamoto, Hidetaka

AU - Suita, Sachiyo

AU - Tsuneyoshi, Masazumi

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