Children's Cancer Research Group, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Br J Cancer. 2013 Jul 9;109(1):195-206. doi: 10.1038/bjc.2013.168. Epub 2013 Jun 25.
Primary Ewing's sarcoma family of tumours (ESFTs) may respond to chemotherapy, although many patients experience subsequent disease recurrence and relapse. The survival of ESFT cells following chemotherapy has been attributed to the development of resistant disease, possibly through the expression of ABC transporter proteins.
MRP-1 and Pgp mRNA and protein expression in primary ESFTs was determined by quantitative reverse-transcriptase PCR (RT-qPCR) and immunohistochemistry, respectively, and alternative splicing of MRP-1 by RT-PCR.
We observed MRP-1 protein expression in 92% (43 out of 47) of primary ESFTs, and cell membrane MRP-1 was highly predictive of both overall survival (P<0.0001) and event-free survival (P<0.0001). Alternative splicing of MRP-1 was detected in primary ESFTs, although the pattern of splicing variants was not predictive of patient outcome, with the exception of loss of exon 9 in six patients, which predicted relapse (P=0.041). Pgp protein was detected in 6% (38 out of 44) of primary ESFTs and was not associated with patient survival.
For the first time we have established that cell membrane expression of MRP-1 or loss of exon 9 is predictive of outcome but not the number of splicing events or expression of Pgp, and both may be valuable factors for the stratification of patients for more intensive therapy.
原发性尤文氏肉瘤家族肿瘤（ESFT）可能对化疗有反应，尽管许多患者随后会出现疾病复发和转移。化疗后 ESFT 细胞的存活归因于耐药性的发展，可能通过 ABC 转运蛋白的表达。
通过定量逆转录 PCR（RT-qPCR）和免疫组织化学分别确定原发性 ESFT 中的 MRP-1 和 Pgp mRNA 和蛋白表达，并通过 RT-PCR 确定 MRP-1 的选择性剪接。
我们观察到 92%（43/47）的原发性 ESFT 中有 MRP-1 蛋白表达，细胞膜 MRP-1 高度预测总生存期（P<0.0001）和无事件生存期（P<0.0001）。在原发性 ESFT 中检测到 MRP-1 的选择性剪接，但剪接变体的模式与患者预后无关，除了 6 例患者中缺失外显子 9 外，后者预测复发（P=0.041）。在 6%（38/44）的原发性 ESFT 中检测到 Pgp 蛋白，与患者生存无关。
我们首次建立了细胞膜 MRP-1 表达或外显子 9 缺失可预测预后，但不是剪接事件的数量或 Pgp 的表达，两者都可能是为更强化疗分层患者的有价值的因素。
