Stromal Lymph Node Involvement Adds to the Prognosis of Stage III Colon Cancer Patients

Background: The tumor microenvironment has ample impact on the behavior of the malignant process in colon cancer (CC). Patients with a high percentage of stromal cells within the primary tumor, determined by the tumor-stroma ratio (TSR), show a poor prognosis. Analysis of this parameter in lymph nodes of stage III CC patients was observed to be a heterogeneous process and may have impact on patients’ prognosis and treatment.

Methods: Primary tumor (PT) and lymph node (LN) tissue slides from 187 patients with stage III colon cancer were analyzed for their TSR. Stroma-high (>50% stroma) and stroma-low (≤50% stroma) groups were evaluated with respect to disease free survival (DFS).

Results: Of 187 analyzed primary tumors, 84 (44.9%) were scored as stroma-high and 103 (55.1%) as stroma-low. In total 53 patients had at least one stroma-high LN, and 134 patients had one or more stroma-low LNs. Interestingly, 44 (23.5%) patients had stroma-high as well as stroma-low LNs, and in another 83 cases the TSR between PT and LNs differed; 57 patients had a stroma-high PT but stroma-low LNs, and 26 patients vice versa. As a result of the combination of the TSR analysis of the PT and the involved LNs, 109 patients (58.3%) were stroma-high and 78 (41.7%) stroma-low, restaging 13.4% patients to stroma-high, with a significantly worse 5-year DFS compared to stroma-low patients [48% versus 66%, p=0.014, HR=1.69 (95%CI 1.11–2.55)].

Conclusion: The analysis of the TSR in LNs revealed the metastasizing process to be very heterogeneous. The presence of abundant stroma in lymph nodes of stage III colon cancer patients adds to the prognostic information of the primary tumor and supports selective treatment.