Tumor stroma percentage (TSP) and intrinsic subtypes in stage II/III colon cancer: NRG Oncology/NSABP C-07 trial.

Abstract

e15075 Background: Recent molecular subtype studies of colorectal cancer (CRC) have identified various genomic signatures. Regardless of the variety of studies, poor prognosis is associated with stem-like or mesenchymal subtypes, which are largely contributed by stromal cells or cancer-associated fibroblasts (CAF) and are driven by transforming growth factor-beta (TGF-ß) signaling. Tumor stroma percentage (TSP) in CRC morphologically evaluated on H&E slides has been reported as an independent prognostic parameter in stage II/III colon cancer patients (pts). We tested the association of TSP with molecular subtypes in NRG Oncology/NSABP C-07, in which pts with a stem-like or mesenchymal subtype had a poor prognosis regardless of chemotherapy regimen. Methods: Ninety seven pts with available archived whole-section H&E images from C-07 were reviewed for TSP for the stromal proportion in the most invasive part of the primary tumor as stroma-high (>50%) or stroma-low (≤50%) as described in other studies. The population was selected to be enriched with stem-like subtype. Subtypes were determined by modified centroids based on Assigner (CRCA) classifier using archived nCounter data, described previously. Results: Of 23 pts, 22 (95.7%) with stroma-high tumor (TSP >50%) were classified with the stem-like subtype. One stroma-high pt had a tumor with a non-stem-like subtype. Of 56 pts with stem-like subtype tumors, 22 were classified as stroma-high, whereas 1/41 with non-stem-like tumors was classified as stroma-high (P=0.00007). Conclusions: TSP is strongly associated with stem-like subtype of poor prognosis in stage II/III CRC and identifies a subset of stem-like subtype. Further study may reveal TSP as a simple biomarker for treatment resistance and potential therapies targeting stromal cells or CAF driven by TGF-ß signaling. SUPPORT: sanofi; U10CA180868, -180822, U24CA196067, PA DoH; NSABP. No. of samples with TSP >50 according to CRCA subtypes. Clinical trial information: NCT00004931. [Table: see text]