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Intratumoral stromal morphometry predicts disease recurrence but not response to 5‐fluorouracil—results from the QUASAR trial of colorectal cancer
Author(s) -
Hutchins Gordon G A,
Treanor Darren,
Wright Alexander,
Handley Kelly,
Magill Laura,
TinklerHundal Emma,
Southward Katie,
Seymour Matthew,
Kerr David,
Gray Richard,
Quirke Philip
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13326
Subject(s) - medicine , colorectal cancer , stage (stratigraphy) , kras , stromal cell , confidence interval , relative risk , oncology , rectum , stroma , cancer , gastroenterology , pathology , biology , immunohistochemistry , paleontology
Aims The biological importance of tumour‐associated stroma is becoming increasingly apparent, but its clinical utility remains ill‐defined. For 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 . Methods and results Relative proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically quantified on digitised haematoxylin and eosin (H&E) sections derived from 1800 patients enrolled in QUASAR , which randomised 3239 (91% stage II ) CRC patients between adjuvant fluorouracil/folinic acid ( FUFA ) chemotherapy and observation. The prognostic and predictive values of PoT/PoS measurements were determined by the use of stratified log‐rank analyses. A high proportion of tumour stroma (≥50%) was associated with an increased recurrence risk: 31.3% (143/457) recurrence for ≥50% versus 21.9% (294/1343) for <50% [rate ratio ( RR ) 1.62; 95% confidence interval ( CI ) 1.30–2.02; P < 0.0001]. Of patients with stromal proportions of ≥65%, 40% (46/115) had recurrent disease within 10 years. The adverse prognostic effect of a high stromal proportion was independent of established prognostic variables, and was 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 a high stromal proportion augmented recurrence risk ( RR 2.93; 95% CI 1.87–4.59; P = 0.0005). Stromal morphometry did not predict response to FUFA chemotherapy. Conclusions Simple digital morphometry applied to a single representative H&E section identifies CRC patients with a >50% higher risk of disease recurrence. This technique can reliably partition patients into subpopulations with different risks of tumour recurrence in a simple and cost‐effective manner. Further prospective validation is warranted.