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Br J Cancer. 2019 Aug;121(4):303-311. doi: 10.1038/s41416-019-0519-1. Epub 2019 Jul 10.

Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer.

Author information

1
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. artur.mezheyeuski@igp.uu.se.
2
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. artur.mezheyeuski@igp.uu.se.
3
City Clinical Pathologoanatomic Bureau, Minsk, Belarus.
4
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
5
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
6
Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Stockholm, Sweden.
7
N.N. Alexandrov National Cancer Centre of Belarus, Minsk, Belarus.

Abstract

BACKGROUND:

Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task.

METHODS:

Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area.

RESULTS:

High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051).

CONCLUSION:

Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.

PMID:
31289351
PMCID:
PMC6738077
[Available on 2020-07-10]
DOI:
10.1038/s41416-019-0519-1

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