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

被引：41

作者：

Bleckmann, Annalen ^{[1
,2
]}

Conradi, Lena-Christin ^{[3
]}

Menck, Kerstin ^{[1
]}

Schmick, Nadine Annette ^{[1
]}

Schubert, Antonia ^{[1
]}

Rietkoetter, Eva ^{[1
]}

Arackal, Jetcy ^{[1
]}

Middel, Peter ^{[4
]}

Schambony, Alexandra ^{[5
]}

Liersch, Torsten ^{[3
]}

Homayounfar, Kia ^{[3
]}

Beissbarth, Tim ^{[2
]}

Klemm, Florian ^{[1
]}

Binder, Claudia ^{[1
]}

Pukrop, Tobias ^{[1
,6
]}

机构：

[1] Univ Med Ctr Gottingen, Dept Med Hematol Oncol, D-37099 Gottingen, Germany

[2] Univ Med Ctr Gottingen, Dept Med Stat, D-37099 Gottingen, Germany

[3] Univ Med Ctr Gottingen, Dept Gen Visceral & Pediat Surg, D-37099 Gottingen, Germany

[4] Univ Med Ctr Gottingen, Inst Pathol, D-37099 Gottingen, Germany

[5] Univ Erlangen Nurnberg, Dept Biol, Dev Biol, D-91058 Erlangen, Germany

[6] Univ Regensburg, Clin Internal Med 3, Hematol & Med Oncol, D-93053 Regensburg, Germany

来源：

CLINICAL & EXPERIMENTAL METASTASIS | 2016年 / 33卷 / 04期

关键词：

Breast cancer; Metastasis; WNT signaling; Prognostic score; BRAIN METASTASES; BRANCHED EVOLUTION; COLORECTAL-CANCER; PRIMARY TUMORS; CELL-LINES; COLONIZATION; PROGRESSION; GROWTH; HETEROGENEITY; DISSEMINATION;

D O I：

10.1007/s10585-016-9780-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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, beta-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 beta-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 beta-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis.

引用

页码：309 / 323

页数：15

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