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| Content Provider | Springer Nature Link |
|---|---|
| Author | Bleckmann, Annalen Conradi, Lena Christin Menck, Kerstin Schmick, Nadine Annette Schubert, Antonia Rietkötter, Eva Arackal, Jetcy Middel, Peter Schambony, Alexandra Liersch, Torsten Homayounfar, Kia Beißbarth, Tim Klemm, Florian Binder, Claudia Pukrop, Tobias |
| Copyright Year | 2016 |
| Abstract | 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. |
| Starting Page | 309 |
| Ending Page | 323 |
| Page Count | 15 |
| File Format | |
| ISSN | 02620898 |
| Journal | Clinical & Experimental Metastasis |
| Volume Number | 33 |
| Issue Number | 4 |
| e-ISSN | 15737276 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2016-02-09 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Breast cancer Metastasis WNT signaling Prognostic score Cancer Research Biomedicine general Oncology Hematology Surgical Oncology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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