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

• Published in: British journal of cancer Vol. 121; no. 4; pp. 303 - 311
• Main Authors: Mezheyeuski, Artur, Hrynchyk, Ina, Herrera, Mercedes, Karlberg, Mia, Osterman, Eric, Ragnhammar, Peter, Edler, David, Portyanko, Anna, Ponten, Fredrik, Sjöblom, Tobias, Glimelius, Bengt, Östman, Arne
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2019; Nature Publishing Group UK
• Subjects: 5-Fluorouracil; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chemotherapy; Colon cancer; Colonic Neoplasms - blood supply; Colonic Neoplasms - drug therapy; Colonic Neoplasms - mortality; Colonic Neoplasms - pathology; Colorectal cancer; Density; Fluorouracil - administration & dosage; Humans; Invasiveness; Medicin och hälsovetenskap; Neoplasm Invasiveness; Neoplasm Staging; Patients; Stroma; Surgery; Tissue analysis; Tumors
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-019-0519-1

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