Journal of Clinical Oncology, Vol 19, Issue 4
(February), 2001: 1128-1136
© 2001 American Society for Clinical Oncology
Molecular Staging of Early Colon Cancer on the Basis of Sentinel Node Analysis: A Multicenter Phase II Trial
By Anton J. Bilchik,
Sukamal Saha,
David Wiese,
James A. Stonecypher,
Thomas F. Wood,
Stuart Sostrin,
Roderick R. Turner,
He-Jing Wang,
Donald L. Morton,
Dave S.B. Hoon
From the Departments of Molecular Oncology, Surgical Oncology and Pathology, John Wayne Cancer Institute, Saint John’s Health Center, Santa Monica, CA; Michigan State University, McLaren Regional Medical Center, Flint, MI; Century City Hospital, Los Angeles, CA; and Department of Biomathematics, University California Los Angeles School of Medicine, Los Angeles, CA.
Address reprint requests to Anton J. Bilchik, MD, PhD, FACS, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404; email: bilchika{at}jwci.org
PURPOSE: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis.
PATIENTS AND METHODS: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: ß-chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10-3 to 10-4 µg of RNA and one to five tumor cells in 107 lymphocytes of healthy donors.
RESULTS: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P < .04) with the T stage of the primary tumor. There was 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs.
CONCLUSION: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.
Presented in part at the American Society of Clinical Oncology, New Orleans, LA, March 2000, and the American Gastroenterology Association, San Diego, CA, May 2000.
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