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Invasion patterns in brain metastases of solid cancers


Berghoff, A S; Rajky, O; Winkler, F; Bartsch, R; Furtner, J; Hainfellner, J A; Goodman, S L; Weller, M; Schittenhelm, J; Preusser, M (2013). Invasion patterns in brain metastases of solid cancers. Neuro-Oncology, 15(12):1664-1672.

Abstract

Background Brain metastases are generally considered to be well demarcated from the surrounding brain parenchyma, although infiltrative growth patterns have been observed. We systemically investigated infiltration patterns and expression of adhesion molecules in a large and well-defined series of autopsy cases of brain metastases. Methods Ninety-seven autopsy specimens from 57 brain metastasis patients (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 2 colorectal cancer, 1 kidney cancer, and 13 other) were evaluated for patterns of invasion into surrounding brain parenchyma. Expression of integrins αv; cytoplasmic β3, αvβ3, αvβ5, αvβ6, and αvβ8; and of E and N cadherin were evaluated using immunohistochemistry. Results Three main invasion patterns were seen: well-demarcated growth (29/57, 51%), vascular co-option (10/57, 18%), and diffuse infiltration (18/57, 32%). There was no statistically significant association of invasion pattern with primary tumor type, although vascular co-option was most common in melanoma brain metastases (4/10). Invasion patterns of different brain metastases of the same patient were highly concordant (P < .001, chi-square test). Distance of infiltration from the main tumor mass ranged from 12.5 µm to 450 µm (median 56.2 µm) and was not significantly different between the vascular co-option and the diffuse infiltration groups. Levels of αvβ6 were significantly higher in the well-demarcated group than in the vascular co-option and the diffuse infiltration groups (P = .033, Kruskal-Wallis test). Expression of αvβ5 in tumor cells was higher in brain metastasis lesions previously treated with stereotactic radiosurgery (P = .034, chi-square test). Conclusions Distinct invasion patterns of brain metastases into the brain parenchyma are not specific for primary tumor types, seem to be influenced by expression of αv integrin complexes, and may help to guide clinical decision-making.

Abstract

Background Brain metastases are generally considered to be well demarcated from the surrounding brain parenchyma, although infiltrative growth patterns have been observed. We systemically investigated infiltration patterns and expression of adhesion molecules in a large and well-defined series of autopsy cases of brain metastases. Methods Ninety-seven autopsy specimens from 57 brain metastasis patients (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 2 colorectal cancer, 1 kidney cancer, and 13 other) were evaluated for patterns of invasion into surrounding brain parenchyma. Expression of integrins αv; cytoplasmic β3, αvβ3, αvβ5, αvβ6, and αvβ8; and of E and N cadherin were evaluated using immunohistochemistry. Results Three main invasion patterns were seen: well-demarcated growth (29/57, 51%), vascular co-option (10/57, 18%), and diffuse infiltration (18/57, 32%). There was no statistically significant association of invasion pattern with primary tumor type, although vascular co-option was most common in melanoma brain metastases (4/10). Invasion patterns of different brain metastases of the same patient were highly concordant (P < .001, chi-square test). Distance of infiltration from the main tumor mass ranged from 12.5 µm to 450 µm (median 56.2 µm) and was not significantly different between the vascular co-option and the diffuse infiltration groups. Levels of αvβ6 were significantly higher in the well-demarcated group than in the vascular co-option and the diffuse infiltration groups (P = .033, Kruskal-Wallis test). Expression of αvβ5 in tumor cells was higher in brain metastasis lesions previously treated with stereotactic radiosurgery (P = .034, chi-square test). Conclusions Distinct invasion patterns of brain metastases into the brain parenchyma are not specific for primary tumor types, seem to be influenced by expression of αv integrin complexes, and may help to guide clinical decision-making.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Date:2013
Deposited On:26 Nov 2013 15:13
Last Modified:07 Dec 2017 23:58
Publisher:Oxford University Press
ISSN:1522-8517
Additional Information:This is a pre-copyedited, author-produced PDF of an article accepted for publication in Neuro-Oncology following peer review. The definitive publisher-authenticated version Berghoff, A S; Rajky, O; Winkler, F; Bartsch, R; Furtner, J; Hainfellner, J A; Goodman, S L; Weller, M; Schittenhelm, J; Preusser, M (2013). Invasion patterns in brain metastases of solid cancers. Neuro-Oncology, 15(12):1664-1672. is available online at: http://neuro-oncology.oxfordjournals.org/content/15/12/1664
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/neuonc/not112
PubMed ID:24084410

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