Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
J Cancer Res Clin Oncol. 2012 Feb;138(2):213-20. doi: 10.1007/s00432-011-1089-7. Epub 2011 Nov 17.
In pediatric alveolar rhabdomyosarcoma, the PAX3-FOXO1 and PAX7-FOXO1 gene fusions are prognostic indicators, while little is known concerning this disease in older patients. To determine whether PAX3/7-FOXO1 fusion gene status correlates with outcome in adolescent, young adult, and adult rhabdomyosarcoma patients, the histological, immunohistochemical, and clinical characteristics of 105 patients followed at The University of Texas MD Anderson Cancer Center from 1957 to 2001 were evaluated.
The samples were assembled into a tissue microarray, and fusion gene status was determined by fluorescence in situ hybridization using PAX3, PAX7, and FOXO1 loci-specific probes. The disease characteristics and specific gene fusion were correlated with patient outcomes using the log-rank test.
Fifty-two percent of the samples exhibited a PAX3-FOXO1 fusion, 15% the PAX7-FOXO1 fusion, and 33% were negative for a rearrangement of these loci. The presence of PAX3/7-FOXO1 translocation was significantly associated with a higher frequency of metastatic disease. Although a statistically significant correlation between the PAX3/7-FOXO1 fusion gene status and overall survival was not identified, there was a trend toward better outcomes for patients with fusion-negative RMS.
Therefore, identification of a FOXO1 fusion appears to be an interesting tool for predicting outcomes in older rhabdomyosarcoma patients and is worth further investigations in this rare subgroup of RMS population.
在儿科肺泡横纹肌肉瘤中，PAX3-FOXO1 和 PAX7-FOXO1 基因融合是预后指标，而对于老年患者的这种疾病知之甚少。为了确定 PAX3/7-FOXO1 融合基因状态是否与青少年、年轻成人和成年横纹肌肉瘤患者的预后相关，评估了 1957 年至 2001 年在德克萨斯大学 MD 安德森癌症中心随访的 105 名患者的组织学、免疫组织化学和临床特征。
将样本组装成组织微阵列，并使用 PAX3、PAX7 和 FOXO1 基因座特异性探针通过荧光原位杂交确定融合基因状态。使用对数秩检验将疾病特征和特定基因融合与患者结局相关联。
52%的样本显示 PAX3-FOXO1 融合，15%显示 PAX7-FOXO1 融合，33%为这些基因座重排阴性。PAX3/7-FOXO1 易位的存在与更高频率的转移性疾病显著相关。尽管未发现 PAX3/7-FOXO1 融合基因状态与总生存率之间存在统计学显著相关性，但融合阴性 RMS 患者的结局有改善趋势。
因此，鉴定 FOXO1 融合似乎是预测老年横纹肌肉瘤患者结局的一种有趣工具，值得在 RMS 人群这一罕见亚组中进一步研究。
