Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial

Clin Cancer Res. 2008 Nov 15;14(22):7391-6. doi: 10.1158/1078-0432.CCR-08-0290.

Abstract

Purpose: Nodal micrometastasis and circulating tumor cells detected by multimarker quantitative real-time reverse transcription-PCR (qRT-PCR) may have prognostic importance in patients with colorectal cancer.

Experimental design: Paraffin-embedded sentinel lymph nodes from 67 patients and blood from 34 of these patients were evaluated in a prospective multicenter trial of sentinel lymph node mapping in colorectal cancer. Sentinel lymph nodes were examined by H&E staining and cytokeratin immunohistochemistry. Sentinel lymph nodes and blood were examined by a four-marker qRT-PCR assay (c-MET, melanoma antigen gene-A3 family, beta1-->4-N-acetylgalactosaminyltransferase, and cytokeratin-20); qRT-PCR results were correlated with disease stage and outcome.

Results: In H&E-negative sentinel lymph node patients that recurred, cytokeratin immunohistochemistry and qRT-PCR detected metastasis in 30% and 60% of patients, respectively. Disease-free survival differed significantly by multimarker qRT-PCR upstaged sentinel lymph node (P = 0.014). qRT-PCR analysis of blood for circulating tumor cells correlated with overall survival (P = 0.040).

Conclusion: Molecular assessment for micrometastasis in sentinel lymph node and blood specimens may help identify patients at high risk for recurrent colorectal cancer, who could benefit from adjuvant therapy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antigens, Neoplasm / biosynthesis
  • Biomarkers, Tumor / analysis*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Keratin-20 / biosynthesis
  • Lymphatic Metastasis / diagnosis*
  • N-Acetylgalactosaminyltransferases / biosynthesis
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / immunology*
  • Polypeptide N-acetylgalactosaminyltransferase
  • Prognosis
  • Proto-Oncogene Proteins c-met / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Sentinel Lymph Node Biopsy

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Keratin-20
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • N-Acetylgalactosaminyltransferases
  • Proto-Oncogene Proteins c-met