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


METHODS
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).


CONCLUSIONS
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.
Koyanagi
Kazuo
K
Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA.
Bilchik
Anton J
AJ
Saha
Sukamal
S
Turner
Roderick R
RR
Wiese
David
D
McCarter
Martin
M
Shen
Perry
P
Deacon
Linda
L
Elashoff
David
D
Hoon
Dave S B
DS
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D053554:Keratin-20 / Q000096:biosynthesis; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D017350:N-Acetylgalactosaminyltransferases / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000276:immunology*; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053554:Keratin-20; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D019859:Proto-Oncogene Proteins c-met; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C072013:MAGEA3 protein, human