Prognostic Significance of Occult Metastases in Colon Cancer

Abstract

The purpose of this study was to determine the prognostic significance of occult lymph node metastases in colon cancer detected by cytokeratin 20 reverse transcription polymerase chain reaction. Two hundred patients undergoing elective colonic resections were enrolled in the study. Lymph nodes from resected specimens were dissected fresh and assessed by both reverse transcription polymerase chain reaction and histopathology. Follow-up was undertaken for up to five years, and the major end point of death was recorded. Univariate survival analysis was performed by the log-rank method and the change-in-estimate method was used to construct multivariate analysis models for the effect of cytokeratin 20 reverse transcription polymerase chain reaction lymph node status on overall survival. A total of 2,317 lymph nodes from 200 patients were assessed by both histopathology and cytokeratin 20 reverse transcription polymerase chain reaction. Forty-eight of 141 (34 percent) histologically lymph node-negative patients had evidence of occult metastases by cytokeratin 20 reverse transcription polymerase chain reaction. An interim analysis was performed at a median of 42 (range, 23-75) months. Cytokeratin 20 reverse transcription polymerase chain reaction lymph node status was a highly significant predictor of overall survival (P < 0.0001) on univariate analysis. In addition, the number of reverse transcription polymerase chain reaction-positive lymph nodes was a significant predictor of survival in the histologically lymph node-negative group (P < 0.0001) on univariate analysis. On multivariate analysis cytokeratin 20 reverse transcription polymerase chain reaction lymph node status had independent prognostic significance for overall survival (P = 0.021; hazard ratio = 2.7) and the number of cytokeratin 20 reverse transcription polymerase chain reaction-positive lymph nodes was a significant predictor of overall survival in the histologically lymph node-negative group (P = 0.005; hazard ratio = 1.1-11.1). Cytokeratin 20 reverse transcription polymerase chain reaction has potential as a clinically useful marker for staging colorectal cancer. Further follow-up is required, but if the current trends continue, a study of the effect of adjuvant therapy in patients with occult metastases detected by cytokeratin 20 reverse transcription polymerase chain reaction is indicated.