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

Mezheyeuski, Artur (author)
Uppsala universitet,Experimentell och klinisk onkologi,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
Hrynchyk, Ina (author)
City Clin Pathologoanat Bur, Minsk, BELARUS
Herrera, Mercedes (author)
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
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Karlberg, Mia (author)
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
Osterman, Eric (author)
Uppsala universitet,Experimentell och klinisk onkologi
Ragnhammar, Peter (author)
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
Edler, David (author)
Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden
Portyanko, Anna (author)
NN Alexandrov Natl Canc Ctr Belarus, Minsk, BELARUS
Pontén, Fredrik (author)
Uppsala universitet,Klinisk och experimentell patologi
Sjöblom, Tobias (author)
Uppsala universitet,Experimentell och klinisk onkologi
Glimelius, Bengt (author)
Uppsala universitet,Experimentell och klinisk onkologi
Ostman, Arne (author)
Karolinska Institutet
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 (creator_code:org_t)
2019-07-10
2019
English.
In: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 121:4, s. 303-311
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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