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Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.ORCID iD: 0000-0002-4394-2634
City Clin Pathologoanat Bur, Minsk, BELARUS.
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
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2019 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 121, no 4, p. 303-311Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 121, no 4, p. 303-311
National Category
Cancer and Oncology
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URN: urn:nbn:se:uu:diva-393661DOI: 10.1038/s41416-019-0519-1ISI: 000480675100003PubMedID: 31289351OAI: oai:DiVA.org:uu-393661DiVA, id: diva2:1354459
Funder
The Cancer Research Funds of RadiumhemmetSwedish Research CouncilAvailable from: 2019-09-25 Created: 2019-09-25 Last updated: 2019-09-25Bibliographically approved

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Mezheyeuski, ArturOsterman, EricPontén, FredrikSjöblom, TobiasGlimelius, Bengt

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