Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's Sarcoma Family of Tumors
Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's Sarcoma Family of Tumors
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DOI：
10.1002/ijc.25424
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发表时间：
2011-03-01
影响因子：
6.4
通讯作者：
Llombart-Bosch, Antonio
中科院分区：
文献类型：
--
作者：
Antonio Lopez-Guerrero, Jose;Machado, Isidro;Llombart-Bosch, Antonio
超过90%的尤文氏肉瘤家族肿瘤（ESFT）在22号染色体上的EWS基因和转录因子的ETS基因家族的各种成员之间表现出特异性染色体重排。基因融合类型和其他继发性遗传改变，主要涉及细胞周期调控因子，已被证明是ESFT的预后相关性。然而，尚未报告任何结论性结果。我们分析了相关细胞周期调节因子在遗传学证实的ESFT中的临床病理意义。应用荧光原位杂交技术检测324例乳腺癌组织中p53、P21（Waf1/CLp1）、p27（Kip1）和Ki67的表达及p53和9p21基因的染色体改变。我们注意到：p53（p = 0.025）、p21（Waf 1/CiP 1）（p = 0.015）和p27（Kip 1）（p = 0.013）在弥漫性疾病中的表达高于局限性疾病。此外，217例局限性疾病患者的队列被认为是研究这些因素对患者随访的预后影响。中位随访时间为39个月（范围：0.17 - 452），总生存率（OS）为55%。Ki67在34%的病例中表达，构成了无进展生存期和OS的独立预后因素，与治疗类型无关[风险比为2.0（95% CI：1.3 - 3.1; p = 0.003）和1.9（95% IC：13 - 23; p = 0.007），在方案计划中纳入放疗的患者组中尤其相关。总之，这项研究表明，1 β 167表达构成了一个有价值的指标，局部ESFT预后不良。
More than 90% of all Ewing's Sarcoma Family of Tumors (ESFT) exhibit specific chromosomal rearrangements between the EWS gene on chromosome 22 and various members of the ETS gene family of transcription factors. The gene fusion type and other secondary genetic alterations, mainly involving cell cycle regulators, have been shown to be of prognostic relevance in ESFT. However, no conclusive results have been reported. We analyzed the clinicopathological significance of relevant cell cycle regulators in genetically confirmed ESFT. A total of 324 cases were analyzed for the immunohistochemical expression of p53, P21(Waf1/CLp1), p27(Kip1) and Ki67 and the chromosomal alterations of the p53 and 9p21 locus by fluorescent in situ hybridization. We observed that: expression of p53 (p = 0.025), p21(Waf1/CiP1) (p = 0.015) and p27(Kip1) (p = 0.013) was higher in disseminated than in localized disease. Furthermore, a cohort of 217 patients with localized disease was considered for studying the prognosis involvement of these factors on patient follow-up. The median follow-up was 39 months (range: 0.17- 452) with an overall survival (OS) of 55%. Ki67 was expressed in 34% of cases and constituted an independent prognostic factor for progression free survival and OS independently of the type of treatment [hazard ratio of 2.0 (95% Cl: 1.3-3.1; p = 0.003) and 1.9 (95% IC: 13-23; p = 0.007) for progression free survival and OS, respectively, being especially relevant in the group of patients which incorporated radiotherapy in their regimen schedules. In conclusion, this study demonstrates that 1(167 expression constitutes a valuable indicator of poor prognosis in localized ESFT.