Predictors of occult nodal metastasis in colon cancer: Results from a prospective multicenter trial

Background: The relationship between primary colon cancer and occult nodal metastases (OMs) detected by cytokeratin immunohistochemistry (CK-IHC) is unknown. We sought to investigate the correlation of clinicopathologic features of colon cancer with OMs and to identify predictors of OM. Methods: Patients with colon cancer from 5 tertiary referral cancer centers enrolled in a prospective trial of staging had standard pathologic analysis performed on all resected lymph nodes (using hematoxylin and eosin staining [H&E]). Nodes negative on H&E underwent CK-IHC to detect OMs, which were defined as micrometastases (N1mic) or isolated tumor cells (N0i+). Patients who were negative on both H&E and CK-IHC were defined as node negative (NN), and those positive on H&E were node positive (NP). The relationships between tumor characteristics and OMs were analyzed using the Kruskal-Wallis and the Fisher exact test. Results: OMs were identified in 23.4% (25/107) of patients. No significant differences were found in demographics, tumor location, tumor size, and number of nodes examined between groups. Compared with the NN group, patients with OMs had more tumors that were T3/T4 (72% vs 57%; P < .001), had tumors of higher grade (28% vs 12%; P = .022), and had tumors with lymphovascular invasion (16% vs 3%; P < .001). Conclusion: Adverse primary pathologic colon cancer characteristics correlate with OMs. In patients with negative nodes on H&E and stage T3/T4 colon cancer, lymphovascular invasion, or high tumor grade, consideration should be given to performing CK-IHC. The detection of OMs in this subset may influence decisions regarding adjuvant chemotherapy and risk stratification.