Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.
Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study.
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DOI：
10.1038/bjc.2014.567
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发表时间：
2014-12-09
影响因子：
8.8
通讯作者：
Kelemen, L. E.
中科院分区：
文献类型：
--
作者：
Koebel, M.;Madore, J.;Ramus, S. J.;Clarke, B. A.;Pharoah, P. D. P.;Deen, S.;Bowtell, D. D.;Odunsi, K.;Menon, U.;Morrison, C.;Lele, S.;Bshara, W.;Sucheston, L.;Beckmann, M. W.;Hein, A.;Thiel, F. C.;Hartmann, A.;Wachter, D. L.;Anglesio, M. S.;Hogdall, E.;Jensen, A.;Hogdall, C.;Kalli, K. R.;Fridley, B. L.;Keeney, G. L.;Fogarty, Z. C.;Vierkant, R. A.;Liu, S.;Cho, S.;Nelson, G.;Ghatage, P.;Gentry-Maharaj, A.;Gayther, S. A.;Benjamin, E.;Widschwendter, M.;Intermaggio, M. P.;Rosen, B.;Bernardini, M. Q.;Mackay, H.;Oza, A.;Shaw, P.;Jimenez-Linan, M.;Driver, K. E.;Alsop, J.;Mack, M.;Koziak, J. M.;Steed, H.;Ewanowich, C.;DeFazio, A.;Chenevix-Trench, G.;Fereday, S.;Gao, B.;Johnatty, S. E.;George, J.;Galletta, L.;Goode, E. L.;Kjaer, S. K.;Huntsman, D. G.;Fasching, P. A.;Moysich, K. B.;Brenton, J. D.;Kelemen, L. E.
叶酸受体1（FOLR 1）在大多数卵巢癌（OvCa）中表达，使其成为有吸引力的治疗靶点。然而，在OvCa中测试抗FOLR 1疗法的临床试验显示了好坏参半的结果，需要更好地了解FOLR 1表达的预后相关性。我们进行了一项大型研究，评估不同组织学类型OvCa中FOLR 1表达与生存率。通过集中免疫组化评估了由卵巢肿瘤组织分析（OTTA）联盟中2801例患者的肿瘤样本组成的组织微阵列的FOLR 1表达。我们使用校正的考克斯回归模型估计了总生存期（OS）和无进展生存期（PFS）的相关性。对来自癌症基因组图谱（TCGA）的高级别浆液性卵巢癌（HGSC）的FOLR 1 mRNA上调与生存率之间的相关性进行独立评价。FOLR 1表达范围从HGSC中的76%到OTTA中粘液癌中的11%。对于HGSC，在OTTA（P相互作用=0.01，N=1422）和TCGA（P相互作用= 0.01，N=485）中，FOLR 1表达与OS之间的相关性在诊断后的几年内发生了显著变化。在OTTA中，特别是对于FIGO I/II期肿瘤，FOLR 1阳性HGSC患者仅在前2年内显示OS增加（风险比=0.44，95%置信区间=0.20-0.96），FOLR 1阳性透明细胞癌（CCC）患者显示PFS降低，与随访时间无关（HR=1.89，95% CI=1.10-3.25，N=259）。在TCGA中，无论肿瘤分期如何，HGSC中FOLR 1 mRNA上调也与诊断后前2年内OS增加相关（HR：0.48，95% CI：0.25-0.94）。FOLR 1阳性HGSC肿瘤与诊断后前2年OS增加相关。FOLR 1阴性、预后不良的HGSC患者不太可能从抗FOLR 1治疗中获益。相比之下，观察到FOLR 1阳性CCC的PFS间期缩短。因此，应根据诊断后的组织学、分期和时间评估FOLR 1靶向干预的临床疗效。
Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20–0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10–3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25–0.94). FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.
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影响因子：
6.4
作者：
He, Wei;Kularatne, Surnith A.;Kalli, Kimberly R.;Prendergast, Franklyn G.;Amato, Robert J.;Klee, George G.;Hartmann, Lynn C.;Low, Philip S.
通讯作者：
Low, Philip S.
影响因子：
4.7
作者：
Koebel, Martin;Kalloger, Steve E.;Swenerton, Kenneth D.
通讯作者：
Swenerton, Kenneth D.
DOI：
10.1097/ede.0b013e3182456ad3
发表时间：
2012-03
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Lo-Ciganic WH;Zgibor JC;Bunker CH;Moysich KB;Edwards RP;Ness RB
通讯作者：
Ness RB
影响因子：
15.9
作者：
KANE, MA;ELWOOD, PC;KOLHOUSE, JF
通讯作者：
KOLHOUSE, JF
影响因子：
4.7
作者：
Kalli, Kimberly R.;Oberg, Ann L.;Hartmann, Lynn C.
通讯作者：
Hartmann, Lynn C.