Takahashi Yukiko, Oda Yoshinao, Kawaguchi Ken-Ichi, Tamiya Sadafumi, Yamamoto Hidetaka, Suita Sachiyo, Tsuneyoshi Masazumi
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mod Pathol. 2004 Jun;17(6):660-9. doi: 10.1038/modpathol.3800101.
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.
横纹肌肉瘤是儿童中最常见的软组织肉瘤。一些报告讨论了横纹肌肉瘤中细胞周期调节蛋白的表达改变和分子异常；然而，已注意到其发生频率各不相同。在本研究中，作者对72例横纹肌肉瘤病例进行了免疫组织化学评估，以检测p53、MDM2、p16、p21/WAF1、p27、细胞周期蛋白D1、细胞周期蛋白E、pRb和E2F-1蛋白的表达，并使用MIB-1评估增殖活性。我们还使用福尔马林固定石蜡包埋材料分析了45例病例中p53基因的突变、18例病例中MDM2基因的扩增以及29例病例中H-ras基因的突变。此外，我们评估了临床病理因素与免疫组织化学和分子分析结果之间的相关性。肺泡型影响年龄较大的患者，与胚胎型相比，其有丝分裂率显著更高（P=0.0226）。在72例病例中有22例（30.6%）检测到p53过表达，45例病例中有10例（22.2%）存在p53基因异常。至于MDM2，在72例病例中有9例（12.5%）发现其过表达，18例病例中有3例（16.7%）显示MDM2扩增。观察到MDM2免疫反应与p53过表达之间存在统计学显著关联（P=0.0002），并且p53和MDM2过表达与高MIB-1标记指数显著相关。与胚胎型相比，肺泡型的E2F-1标记指数得分显著更高（P=0.0334），但MIB-1并非如此。总之，我们的研究表明p53过表达可能与肿瘤进展相关，因为在本研究中p53过表达的肿瘤具有高增殖活性。与胚胎型相比，肺泡型的有丝分裂率和E2F-1标记指数均显著更高。本研究是关于E2F-1与肺泡横纹肌肉瘤相关性的首次报告。
