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Oncotarget. 2016 Jul 5;7(27):41948-41958. doi: 10.18632/oncotarget.9632.

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer.

Author information

1
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
2
Department of Pathology, Belarusian State Medical University, Minsk, Belarus.
3
Department of Oncology, Oslo University Hospital, Oslo, Norway.
4
K.G.Jebsen Colorectal Cancer Research Center, Oslo University Hospital, Oslo, Norway.
5
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
6
Department of Oncology, University of Southern Denmark, Odense, Denmark.
7
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
8
Akershus University Hospital, Lørenskog, Norway.
9
School of Pharmacy, University of Oslo and the Norwegian Institute of Public Health, Oslo, Norway.
10
Division of Translational Cancer Research, Lund University, Lund, Sweden.
11
Department of Neuroscience, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
12
Department of Oncology, Haukeland University Hospital, Bergen, Norway.

Abstract

Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-β or α-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-α and -β and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-α and -β remained independent factors for survival in multivariate analyses.Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-α and -β were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections.

KEYWORDS:

PDGFR; cancer associated fibroblasts; colorectal cancer; perivascular cells; tumor stroma

PMID:
27248825
PMCID:
PMC5173107
DOI:
10.18632/oncotarget.9632
[Indexed for MEDLINE]
Free PMC Article

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