β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases.
β-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases.
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DOI：
10.1007/s10585-016-9780-3
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发表时间：
2016-04
影响因子：
4
通讯作者：
Pukrop T
中科院分区：
文献类型：
--
作者：
Bleckmann A;Conradi LC;Menck K;Schmick NA;Schubert A;Rietkötter E;Arackal J;Middel P;Schambony A;Liersch T;Homayounfar K;Beißbarth T;Klemm F;Binder C;Pukrop T
乳腺癌患者发生肝转移是很常见的，预后很差。到目前为止，手术切除的预后意义和转移组织中生物标记物分析的临床相关性几乎没有被研究过。我们先前证明了WNT信号在乳腺癌脑转移中的作用。本研究旨在探讨已建立的预后标志物和WNT信号成分在肝转移中的价值。总体而言，34例乳腺癌肝转移(19/34例有匹配的原发病例)纳入了这项回顾研究。采用免疫组织化学方法检测原发灶和转移灶中雌激素受体(ER)、孕激素受体、HER-2、Ki67和多种WNT信号成分的表达。此外，还产生了β-连环蛋白依赖和独立的WNT评分，并分析了它们的预后价值。此外，在体外还分析了WNT受体的替代对信号转导和侵袭力的影响。ER阳性(HR 0.09，95%CI 0.01~0.56)和Ki67高表达(HR 3.68，95%CI 1.12~12.06)对预后有影响。然而，转移组织中仅Ki67对预后有预测作用(HR 2.46，95%CI 1.11~5.44)。此外，只有在转移的情况下，β-连环蛋白非依赖性的WNT评分才与总存活率降低相关(HR2.19，95%可信区间1.02-4.69，P=0.0391)。这与促进侵袭的替代WNT受体ROR1和ROR2的体外结果一致。在乳腺癌中，在原发肿瘤中建立的预后标记物的价值不能直接转化为转移。我们的结果显示，在乳腺癌肝转移患者中，β-连环蛋白非依赖性的WNT信号与预后不良有关。本文的在线版本(doi：10.1007/s10585-0169780-3)包含补充材料，授权用户可以使用。
Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER-2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, β-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01–0.56) and high Ki67 (HR 3.68, 95 % CI 1.12–12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11–5.44). Additionally, the β-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02–4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed β-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis. The online version of this article (doi:10.1007/s10585-016-9780-3) contains supplementary material, which is available to authorized users.