Folate receptor alpha as a tumor target in epithelial ovarian cancer
Folate receptor alpha as a tumor target in epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2007.11.020
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发表时间：
2008-03-01
影响因子：
4.7
通讯作者：
Hartmann, Lynn C.
中科院分区：
文献类型：
--
作者：
Kalli, Kimberly R.;Oberg, Ann L.;Hartmann, Lynn C.
目标。叶酸受体α (FR α)是一种叶酸结合蛋白，在卵巢和其他几种上皮恶性肿瘤中过表达，可作为成像和治疗策略的靶点。本研究的目的是改善缺乏FR α在罕见组织学亚型、原发疾病与转移灶以及复发疾病中表达特异性信息的历史数据。通过免疫组织化学分析了186例原发卵巢肿瘤和27例复发性卵巢肿瘤的FR α表达，其中包括24对来自同一个体的诊断和二次减体积手术样本。对186例原发病例中的20例，也分析了同时转移灶。FR - α染色根据疾病形态、分期、分级、减积情况、从诊断到复发和死亡的时间进行分析。在186例原发性卵巢肿瘤中134例（72%）和27例复发性卵巢肿瘤中22例（81.5%）有明显的FR - α表达。在24例匹配标本中，21例（87.5%）的复发肿瘤反映了诊断时检测到的FR α状态。FR - α染色显示转移灶与原发肿瘤相似。在单变量或多变量分析中，FR α状态与复发时间或总生存期无关。FR - α表达频繁发生，特别是在常见的高级别、高分期浆液性肿瘤中，这些肿瘤最容易复发。这项研究的新发现表明FR α在转移灶和复发肿瘤中保持表达，这表明新的叶酸靶向治疗可能对大多数新诊断或复发的卵巢癌妇女有希望。(C) 2007爱思唯尔公司版权所有。
Objectives. Folate receptor alpha (FR alpha) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FR alpha expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.Methods. FR alpha expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FR alpha staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.Results. FR alpha expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FR alpha status detected at diagnosis. Metastatic foci were similar to primary tumors in FR alpha staining. FR alpha status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.Conclusion. FR alpha expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FR alpha expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer. (C) 2007 Elsevier Inc. All rights reserved.