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Visualising and quantifying angiogenesis in metastatic colorectal cancer

A comparison of methods and their predictive value for chemotherapy response

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Abstract

Purpose

Angiogenesis plays an important role in tumour growth and dissemination. We have recently shown that blood vessel density, determined by image analysis based on microRNA-126 (miRNA-126) in situ hybridization (ISH) in the primary tumours of metastatic colorectal cancers (mCRC), is predictive of chemotherapy response. Here, we evaluated whether more general approaches to determine vessel density in primary tumours are equally predictive of chemotherapy response.

Methods

This methodological study was carried out using paraffin embedded tissues from primary tumours of 89 patients with mCRC, who had all been treated with first-line chemotherapy (XELOX). Tissue sections from the deepest invasive tumour front were processed for miRNA-126 ISH and CD34 immunohistochemistry (IHC). Estimates of microvessel density (MVD) were obtained for both miRNA-126 and CD34 by quantitative image analyses (MVDi), vascular area per image (μm2) analyses, and manually counting vessels in vascular hot spots (MVDh). Clinical responses were evaluated according to Response Evaluation Criteria In Solid Tumours (RECIST).

Results

The MVDi for miRNA-126 showed a significant correlation with treatment response (p = 0.01), with a median value of 2,071 μm2 (95 % CI, 1,505–3,075 μm2) in the responder group compared to 1,337 μm2 (95 % CI, 1,038–1,499 μm2) in the non-responder group. This difference translated into a significant difference in progression free survival (p = 0.01).

Conclusions

The methodological assessment of MVD and the molecular vessel marker are both important for the prediction of the chemotherapy response in mCRC. Our findings indicate that MVDi for miRNA-126 represents a powerful estimate and may serve as a clinical biomarker superior to MVDh.

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Acknowledgments

We are very thankful for the technical assistance provided by Birgit Roed Sørensen and Stine Jørgensen, and for the linguistic editing provided by Karin Larsen. Furthermore, René dePont Christensen is acknowledged for statistical counselling. This study was supported by The Cancer Foundation and The Danish Council for Independent Research, which did not affect any part of the study.

Conflict of interest

The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Oncology, Vejle Hospital, Vejle, Denmark

    Torben Frøstrup Hansen & Anders Jakobsen

  2. Bioneer A/S, Hørsholm, Denmark

    Boye Schnack Nielsen

  3. Department of Clinical Pathology, Vejle Hospital, Vejle, Denmark

    Flemming Brandt Sørensen

  4. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

    Torben Frøstrup Hansen, Anders Jakobsen & Flemming Brandt Sørensen

  5. Danish Colorectal Cancer Group South, Vejle, Denmark

    Torben Frøstrup Hansen, Anders Jakobsen & Flemming Brandt Sørensen

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  1. Torben Frøstrup Hansen
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Correspondence to Torben Frøstrup Hansen.

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Hansen, T.F., Nielsen, B.S., Jakobsen, A. et al. Visualising and quantifying angiogenesis in metastatic colorectal cancer. Cell Oncol. 36, 341–350 (2013). https://doi.org/10.1007/s13402-013-0139-3

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