Angiogenesis-promoting gene patterns in alveolar soft part sarcoma
Angiogenesis-promoting gene patterns in alveolar soft part sarcoma
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DOI：
10.1158/1078-0432.ccr-07-0174
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发表时间：
2007-12-15
影响因子：
11.5
通讯作者：
Lev, Dina
中科院分区：
文献类型：
--
作者：
Lazar, Alexander J. F.;Das, Parimal;Lev, Dina
目的：我们检查了在我们机构接受治疗的一组肺泡软组织肉瘤 (ASPS) 患者，并在他们的肿瘤中显示了特征性的 ASPSCR1-TFE3 融合转录本。对潜在血管生成调节分子决定因素的研究为这种不寻常肿瘤的血管分布增强特征提供了机制和潜在治疗相关的见解。 实验设计：对德克萨斯大学 M.D. 安德森癌症中心 (1986-2005) 就诊的 71 名 ASPS 患者的医疗记录进行了审查，以分离出 33 名具有福尔马林固定石蜡包埋材料的患者可供研究。使用逆转录-PCR 和血管生成寡芯片并进行免疫组织化学确认，分析从新鲜冷冻和福尔马林固定石蜡包埋的人 ASPS 肿瘤中提取的 RNA 的 ASPSCR1-TFE3 融合转录本表达。结果：与之前的研究类似，尽管经常发生转移，但精算的 5 年和 10 年生存率分别为 74% 和 51%。在 18 个 ASPS 样本中的 16 个样本中鉴定出了 ASPSCR1-TFE3 融合转录本。在进行血管生成寡阵列分析的三个冷冻样本中，肿瘤中的 18 个血管生成相关基因比邻近的正常组织上调。 33 份人类 ASPS 样本中 jag-1、midkine 和血管生成素的免疫组织化学证实了这些结果。与其他肉瘤的比较表明，ASPS 的血管生成特征是独特的。结论：ASPS 是一种高度血管化和转移性肿瘤，具有令人惊讶的良好结果；治疗耐药性转移会导致死亡率增加。未来针对过度表达的血管生成促进蛋白（例如此处鉴定的蛋白）的分子疗法可能会使 ASPS 患者受益。
Purpose: We examined a cohort of patients with alveolar soft part Sarcoma (ASPS) treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion transcript in their tumors. Investigation of potential angiogenesis-modulating molecular determinants provided mechanistic and potentially therapeutically relevant insight into the enhanced vascularity characteristic of this unusual tumor.Experimental Design: Medical records of 71 patients with ASPS presenting at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed to isolate 33 patients with formalin-fixed paraffin-embedded material available for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin-embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript expression using reverse transcription-PCR and by angiogenesis oligomicroarrays with immunohistochemical confirmation.Results: Similar to previous studies, actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18 ASPS samples. In the three frozen samples subjected to an angiogenesis oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin in 33 human ASPS samples confirmed these results. Comparison with other sarcomas indicates that the ASPS angiogenic signature is unique.Conclusion: ASPS is a highly vascular and metastatic tumor with a surprisingly favorable outcome; therapeutically resistant metastases drive mortality. Future molecular therapies targeting overexpressed angiogenesis-promoting proteins (such as those identified here) could benefit patients with ASPS.