Prognostic Relevance of Occult Metastases Detected by Cytokeratin 20 and Mucin 2 mRNA Levels in Sentinel Lymph Nodes from Colon Cancer Patients

Abstract

To investigate the prognostic value of occult metastases detected by quantitative measurements of candidate biomarkers in sentinel lymph nodes (SLNs) from patients curatively resected for colon cancer. Resection specimens from consecutive patients undergoing surgery for localized colon cancer were subjected to ex vivo SLN mapping. SLNs were examined for the presence of metastases by routine hematoxylin-erythrosin-safranin staining and by cytokeratin 20 (CK20) and mucin 2 (MUC2) mRNA quantification. The patients were stratified according to KRAS and BRAF mutation status and microsatellite instability status in their primary tumors. Survival end points were analyzed by Kaplan-Meier survival estimates and log-rank tests. A total of 817 SLNs were identified in 206 (97%) of the 213 included patients. Routine histological examination of SLNs and other regional lymph nodes identified 63 patients with positive nodes (pN+), of which 42 (67%) were positive in one or more SLNs (sensitivity 67%, false-negative rate 33%). On the basis of the CK20 and MUC2 mRNA levels in SLNs, occult metastases were suggested in 86 (60%) and 52 (36%) of the 143 otherwise LN-negative (pN0) patients, respectively. Survival analysis with a median 3.6-year follow-up revealed that MUC2 mRNA quantification had significant prognostic value in SLNs from all patients; however, occult SLN metastasis detection did not. Occult SLN metastases detected by CK20 and MUC2 mRNA quantification had limited prognostic value.