The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study

2015 | journal article. A publication with affiliation to the University of Göttingen.

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​The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study​
Siam, L.; Bleckmann, A.; Chaung, H.-N.; Mohr, A.; Klemm, F.; Barrantes-Freer, A. & Blazquez, R. et al.​ (2015) 
Oncotarget6(30) pp. 29254​-29267​.​ DOI: https://doi.org/10.18632/oncotarget.4201 

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Authors
Siam, Laila; Bleckmann, Annalen; Chaung, Han-Ning; Mohr, Alexander; Klemm, Florian; Barrantes-Freer, Alonso; Blazquez, Raquel; Wolff, Hendrik Andreas; Lueke, Florian; Rohde, Veit; Stadelmann, Christine ; Pukrop, Tobias
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.
Issue Date
2015
Status
published
Publisher
Impact Journals Llc
Journal
Oncotarget 
ISSN
1949-2553

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