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Local Recurrence in Mismatch Repair–Proficient Colon Cancer Predicted by an Infiltrative Tumor Border and Lack of CD8⁺ Tumor-Infiltrating Lymphocytes

Authors' Affiliation: Institute of Pathology, University Hospital of Basel, Basel, Switzerland

Requests for reprints: Inti Zlobec, Institute of Pathology, University Hospital of Basel, Schönbeinstrasse 40, CH-4031 Basel, Switzerland. Phone: 41-61-265-28-95; Fax: 41-61-265-29-66; E-mail: izlobec{at}uhbs.ch.

Purpose: The identification of colon cancer patients at high risk of local recurrence is necessary to improve the selection of patients for more tailored treatment protocols. The aim of this study was to develop a predictive model of local recurrence by assessing the independent predictive effect of 7 clinicopathologic features, 24 protein markers of tumor progression, and their multifeature combinations in mismatch repair–proficient colon cancers.

Experimental Design: Immunohistochemistry for 24 protein markers was done on 269 patients with complete clinicopathologic data. After univariate and multivariable analyses, independent predictors of local recurrence were identified and their multifeature combinations were analyzed. Kaplan-Meier and Cox proportional hazards regression were done for survival analysis.

Results: Local recurrence was observed in 119 patients (55.8%). Independent predictors of tumor recurrence were lymph node involvement (P = 0.006), absence of CD8⁺ tumor-infiltrating lymphocytes (TIL; P < 0.001), and infiltrative tumor margin (P < 0.001). This independent effect persisted after adjusting for adjuvant therapy. Risk of recurrence was 0.75 and the 5-year survival rate was 8.8% in patients with these three adverse features. Node-negative patients with an infiltrative tumor margin and absence of CD8⁺ TILs were identified as high risk with a probability of 0.55 for recurrence and a 60% 5-year survival rate. The remaining node-negative cases fared significantly better with risks ranging from 8% to 26% and 5-year survival rates reaching 97.6%.

Conclusions: An infiltrative tumor margin and absence of CD8⁺ TILs are highly predictive of local recurrence in node-negative mismatch repair–proficient colon cancer and may help to identify high-risk patients who may benefit from adjuvant chemotherapy.