Siam, Laila and Bleckmann, Annalen and Chaung, Han-Ning and Mohr, Alexander and Klemm, Florian and Barrantes-Freer, Alonso and Blazquez, Raquel and Wolff, Hendrik A. and Lueke, Florian and Rohde, Veit and Stadelmann, Christine and Pukrop, Tobias (2015) The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study. ONCOTARGET, 6 (30). pp. 29254-29267. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
The current approach to brain metastases resection is macroscopic removal of metastasis until reaching the glial pseudo-capsule (gross total resection (GTR)). However, autopsy studies demonstrated infiltrating metastatic cells into the parenchyma at the metastasis/brain parenchyma (M/BP)-interface. Aims/Methods: To analyze the astrocyte reaction and metastatic infiltration pattern at the M/BP-interface with an organotypic brain slice coculture system. Secondly, to evaluate the significance of infiltrating metastatic tumor cells in a prospective biopsy study. Therefore, after GTR, biopsies were obtained from the brain parenchyma beyond the glial pseudo-capsule and analyzed histomorphologically. Results: The coculture revealed three types of cancer cell infiltration. Interestingly, the astrocyte reaction was significantly different in the coculture with a benign, neuroectodermal-derived cell line. In the prospective biopsy study 58/167 (34.7%) samples revealed infiltrating metastatic cells. Altogether, 25/39 patients (64.1%) had proven to exhibit infiltration in at least one biopsy specimen with significant impact on survival (OS) (3.4 HR; p = 0.009; 2-year OS was 6.6% versus 43.5%). Exceptionally, in the non-infiltrating cohort three patients were long-term survivors. Conclusions: Metastatic infiltration has a significant impact on prognosis. Secondly, the astrocyte reaction at the M/BP-interface is heterogeneous and supports our previous concept of the organ-specific defense against metastatic (organ-foreign) cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BRAIN METASTASIS; BREAST-CANCER; BETA-CATENIN; CELLS; MELANOMA; CHEMOTHERAPY; INVASION; TISSUE; astrocytes; brain metastasis; glial-pseudo capsule; metastatic infiltration; organ-specific defense |
| 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: | 16 May 2019 12:31 |
| Last Modified: | 16 May 2019 12:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4630 |
Actions (login required)
 |
View Item |
