The Metastatic Infiltration at the Metastasis/brain Parenchyma-interface is Very Heterogeneous and Has a Significant Impact on Survival in a Prospective Study

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Aug 25

PMID 26299612

Citations 51

Authors

Laila Siam

Annalen Bleckmann

Han-Ning Chaung

Alexander Mohr

Florian Klemm

Alonso Barrantes-Freer

Raquel Blazquez

Hendrik A Wolff

Florian Luke

Veit Rohde

Christine Stadelmann

Tobias Pukrop

Affiliations

Soon will be listed here.

Abstract

Unlabelled: 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.

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