Bleckmann, Annalen and Conradi, Lena-Christin and Menck, Kerstin and Schmick, Nadine Annette and Schubert, Antonia and Rietkoetter, Eva and Arackal, Jetcy and Middel, Peter and Schambony, Alexandra and Liersch, Torsten and Homayounfar, Kia and Beissbarth, Tim and Klemm, Florian and Binder, Claudia and Pukrop, Tobias (2016) beta-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. CLINICAL & EXPERIMENTAL METASTASIS, 33 (4). pp. 309-323. ISSN 0262-0898, 1573-7276
Full text not available from this repository. (Request a copy)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, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BRAIN METASTASES; BRANCHED EVOLUTION; COLORECTAL-CANCER; PRIMARY TUMORS; CELL-LINES; COLONIZATION; PROGRESSION; GROWTH; HETEROGENEITY; DISSEMINATION; Breast cancer; Metastasis; WNT signaling; Prognostic score |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2019 13:56 |
| Last Modified: | 25 Mar 2019 13:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3181 |
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