Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jun 7;104(12):1877-81.
doi: 10.1038/bjc.2011.147. Epub 2011 May 3.

Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases

A M Jubb  1 , A Cesario, M Ferguson, M T Congedo, K C Gatter, F Lococo, A Mulè, F Pezzella
Affiliations

Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases

A M Jubb et al. Br J Cancer. .

Abstract

Background: Anti-angiogenic therapy with bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) predominantly targets immature blood vessels. Bevacizumab has shown a survival benefit in non-small cell lung carcinoma (NSCLC) and has recently been demonstrated to be safe in patients with brain metastases. However, it is not known whether bevacizumab is effective against brain metastases or whether metastases are representative of their primary in terms of VEGF expression, hypoxia, proliferation and vascular phenotype. The aim of this study was to evaluate these factors in a series of matched primary NSCLCs and brain metastases.

Methods and results: Immunohistochemistry showed strong correlation of carbonic anhydrase 9 expression (a marker of hypoxia) in primary and secondary cancers (P=0.0002). However, the proliferation index, VEGF expression, microvessel density and the proportion of mature vessels were discordant between primary and secondary cancers. The mean proportion of mature vessels was 63.2% higher in the brain metastases than the primary tumours (P=0.004). Moreover, the vascular pattern of the primary tumour was not representative of the metastasis.

Conclusions: Brain metastases have a significantly higher proportion of mature vasculature, suggesting that they may be refractory to anti-VEGF therapy. These findings may have implications for clinical trials and biomarker studies evaluating anti-angiogenic agents in brain metastases.

PubMed Disclaimer

Conflict of interest statement

Dr Adrian M Jubb received a speaker's honorarium in 2010 from Genentech Inc., which is developing anti-angiogenic therapies.

Figures

Figure 1
Figure 1
(A) A scatter plot of CD34 Chalkley counts in matched primary (lung) and secondary (brain) cancers. (B) A line plot showing differences in the percentage of blood vessels covered by pericytes in matched primary and secondary cancers. (C) A scatter plot of the percentage of matched primary and secondary cancers positive for carbonic anhydrase 9. (D) A line plot showing differences in the VEGF score in matched primary and secondary cancers. (E, F) Double-labelled immunohistochemistry for CD34 (blue) and smooth muscle actin (brown) in a matched primary (E) and secondary (F) cancer.
See this image and copyright information in PMC

References

    1. Besse B, Lasserre SF, Compton P, Huang J, Augustus S, Rohr UP (2010) Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res 16: 269–278 - PubMed
    1. Fox SB, Leek RD, Weekes MP, Whitehouse RM, Gatter KC, Harris AL (1995) Quantitation and prognostic value of breast cancer angiogenesis: comparison of microvessel density, Chalkley count, and computer image analysis. J Pathol 177: 275–283 - PubMed
    1. Gerstner ER, Frosch MP, Batchelor TT (2010) Diffusion magnetic resonance imaging detects pathologically confirmed, nonenhancing tumor progression in a patient with recurrent glioblastoma receiving bevacizumab. J Clin Oncol 28: e91–e93 - PubMed
    1. Giatromanolaki A, Koukourakis MI, Sivridis E, Pastorek J, Wykoff CC, Gatter KC, Harris AL (2001) Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer. Cancer Res 61: 7992–7998 - PubMed
    1. Grothey A, Hedrick EE, Mass RD, Sarkar S, Suzuki S, Ramanathan RK, Hurwitz HI, Goldberg RM, Sargent DJ (2008) Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. J Clin Oncol 26: 183–189 - PubMed

Publication types

MeSH terms