de Alava E, Kawai A, Healey J H, Fligman I, Meyers P A, Huvos A G, Gerald W L, Jhanwar S C, Argani P, Antonescu C R, Pardo-Mindan F J, Ginsberg J, Womer R, Lawlor E R, Wunder J, Andrulis I, Sorensen P H, Barr F G, Ladanyi M
Clinica Universitaria de Navarra, Pamplona, Spain.
J Clin Oncol. 1998 Apr;16(4):1248-55. doi: 10.1200/JCO.1998.16.4.1248.
More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance.
We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage.
Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis.
EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon.
超过90%的尤因肉瘤（ES）因t(11;22)(q24;q12)易位而含有EWS和FLI1基因融合。在分子水平上，EWS-FLI1重排表现出很大的多样性。具体而言，EWS和FLI1外显子的许多不同组合编码框内融合转录本，并导致嵌合蛋白的长度和组成存在差异，该嵌合蛋白作为一种致癌性异常转录因子发挥作用。在最常见的融合类型（1型）中，EWS外显子7与FLI1外显子6框内连接。作为ES的基本致病病变，这些融合转录本的分子异质性可能具有功能和临床意义。
我们对112例ES患者进行了临床和病理分析，通过逆转录聚合酶链反应（RT-PCR）鉴定出EWS-FLI1融合转录本。99例接受根治性治疗的患者有充分的治疗和随访数据。这99例患者的中位随访时间为26个月（范围1至140个月）。进行了单因素和多因素生存分析，纳入了其他预后因素，如年龄、肿瘤部位、大小和分期。
在99例适合生存分析的患者中，64例患者的肿瘤含有1型融合，35例患者的肿瘤含有较罕见的融合类型。初诊时分期为局限性的患者有74例，转移性的有25例。多因素分析显示，转移（相对风险[RR]=2.6；P=0.008）和1型EWS-FLI1融合（RR=0.37；P=0.014）分别是总生存的独立负性和正性预后因素。在74例局限性肿瘤患者中，多因素分析显示1型EWS-FLI1融合也是总生存的显著正性预测因素（RR=0.32；P=0.034）。
EWS-FLI1融合类型在ES中似乎与预后相关，独立于肿瘤部位、分期和大小。需要进一步研究以阐明这一现象的生物学基础。
Zotero 插件