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Stroma-High Lymph Node Involvement Predicts Poor Survival More Accurately for Patients with Stage III Colon Cancer

Gabi W van Pelt, Torben F Hansen, Esther Bastiaannet, Sanne Kjær-Frifeldt, J Han JM van Krieken, Rob AEM Tollenaar, Flemming B Sørensen, Wilma E Mesker

Objective: The tumor microenvironment has ample impact on the behavior of the malignant process in colon cancer (CC). Patients with a high percentage of stroma within the primary tumor, determined by the tumor-stroma ratio (TSR), have a poor prognosis. In metastatic lymph nodes from patients with stage III CC, the TSR is heterogeneous, but the impact on patients’ prognosis is unknown.
Methods: Haematoxylin and eosin stained tissue slides of primary tumor (PT) and associated lymph nodes (LNs) metastases from 102 patients with stage III CC were analyzed for the TSR. Stroma-high (>50% stroma) and stromalow (≤ 50% stroma) groups were evaluated with respect to disease free survival (DFS).
Results: Of 102 analyzed primary tumors, 47 (46.1%) scored as stroma-high and 55 (53.9%) as stroma-low. In total, 33 patients had at least one stroma-high LN and 69 patients had one or more stroma-low LNs. Interestingly, 28 patients (27.5%) had both stroma-high and stroma-low LNs, but in another 44 cases the TSR between PT and LNs differed: 29 patients had a stroma-high PT with stroma-low LNs, while 15 patients displayed the opposite. As a result of the combination of the TSR analysis of the PT and the involved metastatic LNs, 62 patients (60.8%) were classified as stroma-high and 40 (39.2%) as stroma-low, restaging 14.7% of the patients to stroma-high with a significantly worse 5-year DFS compared to stroma-low patients (59% vs. 82%, HR=2.83 (95%CI 1.34–5.97), P=0.006). In multivariate analysis, the TSR retained its independent prognostic impact (HR=2.85 (95%CI 1.33-6.10), P=0.007).
Conclusion: The presence of abundant stroma in metastatic LNs from patients with stage III CC adds to the prognostic information learned from the primary tumor independently, and supports selective patient treatment.