Hutchins, GGA orcid.org/0000-0002-1707-4415, Treanor, D orcid.org/0000-0002-4579-484X, Wright, A et al. (9 more authors) (2018) Intra-tumoural stromal morphometry predicts disease recurrence but not response to 5-fluorouracil – results from the QUASAR trial of colorectal cancer. Histopathology, 72 (3). pp. 391-404. ISSN 0309-0167
Abstract
Introduction: The biological importance of tumour-associated stroma is increasingly apparent, yet clinical utility remains ill-defined. In stage-II / Dukes B colorectal cancer (CRC), clinical biomarkers are urgently required to direct therapeutic options. We report here prognostic/predictive analyses, and molecular associations, of stromal morphometric quantification in the Quick and Simple and Reliable (QUASAR) trial of CRC. Materials and methods: Relative proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically quantified using digitised haematoxylin and eosin sections derived from 1,800 patients enrolled in QUASAR which randomised 3,239 (91% stage II) CRC patients between adjuvant fluorouracil/folinic acid (FUFA) chemotherapy and observation. The prognostic/predictive value of PoT/PoS measures were determined by stratified log-rank analyses. Results: High tumour stroma (≥50%) was associated with increased recurrence risk: 31.3% (143/457) recurrence for ≥50% versus 21.9% (294/1,343) if <50% [Rate ratio (RR)=1.62; 95%CI 1.30-2.02, p<0.0001)]. For stromal proportions of ≥65%, 40% (46/115) of patients had recurrent disease within 10 years. The adverse prognostic effect of high stroma was independent of established prognostic variables, and maintained in stage II / Dukes B patients (RR=1.62; 95%CI=1.26-2.08; p=0.0002). KRAS mutation in the presence of high stroma augmented recurrence risk (RR=2.93; 95%CI=1.87-4.59; p=0.0005). Stromal morphometry did not predict response to FUFA chemotherapy. Discussion: Simple digital morphometry applied to a single representative H&E section identifies CRC patients with over 50% higher risk of disease recurrence. This technique can reliably partition patients into sub-populations with differential risks of tumour recurrence in a simple and cost-effective manner. Further prospective validation is warranted.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2017 John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Hutchins, Gordon. G.A., Treanor, D., Wright, A., Handley, K., Magill, L., Tinkler-Hundal, E., Southward, K., Seymour, M., Kerr, D., Gray, R., Quirke, P. and The QUASAR trial collaborators the UK National Cancer Research Institute Colorectal Cancer Clinical Studies Group (2017), Intra-tumoural stromal morphometry predicts disease recurrence but not response to 5-fluorouracil – results from the QUASAR trial of colorectal cancer. Histopathology. Accepted Author Manuscript. doi:10.1111/his.13326, which has been published in final form at https://doi.org/10.1111/his.13326. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Colon; Colorectal; Rectal; Cancer; Stroma |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Funding Information: | Funder Grant number Yorkshire Cancer Research L354 PA |
Depositing User: | Symplectic Publications |
Date Deposited: | 31 Jul 2017 10:26 |
Last Modified: | 26 Jul 2018 00:38 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/his.13326 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119656 |