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Prognostic Relevance of Occult Nodal Micrometastases and Circulating Tumor Cells in Colorectal Cancer in a Prospective Multicenter Trial

Authors' Affiliations: ¹ Department of Molecular Oncology, John Wayne Cancer Institute, and ² Department of Surgical Pathology, Saint John's Health Center, Santa Monica, California; ³ McLaren Regional Medical Center, Michigan State University, Flint, Michigan; ⁴ Department of Surgery, University of Colorado Health Science Center, Denver, Colorado; ⁵ Department of Surgical Oncology, Wake Forest University Medical Center, Winston-Salem, North Carolina; and ⁶ Department of Biostatistics, School of Medicine, University of California, Los Angeles, Los Angeles, California

Requests for reprints: Dave S.B. Hoon, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404. Phone: 310-449-5282; Fax: 310-449-5282; E-mail: hoon{at}jwci.org.

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, β14-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.