Genetic Detection of Circulating Cancer Cells and Micrometastasis in the Lymph Node

Shoji Nakamori, Masao Kameyama, Shingi Imaoka, Takushi Yasuda, Toshiyuki Kabuto, Masahiro Hiratsuka, Hiroshi Furukawa, Hiroaki Ohigashi, Osamu Ishikawa, Tomohiko Aihara, Hiroshi Nakano, Yo Sasaki, Takeshi Iwanaga, Osamu Takeda¹⁾, Yusuke Nakamura²⁾

The First Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases
Takara Advanced Biomedical Center¹⁾, Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, and Division of Clinical Genetics, Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School²⁾

We investigated the possibility of genetically detecting the rare colorectal cancer cells in blood and lymph nodes histologically negative for metastasis. Using an RT-PCR assay system for the detection of rare circulating colorectal cancer cells, employing cytokeratin (CK) mRNA expression as a marker, four of 22 samples were found to be positive for CK. One stage II patient and three stage IV patients were positive for CK in drainage-vein blood. One of the three stage IV patients was positive for CK in both drainage-vein and peripheral blood. None of the d22 samples examined were immunocytologically negative for anti-CK antibody. We also screened 109 colorectal cancers from patients without histologically detectable lymph node metastasis for mutations of the K-ras or p53 oncogene and identified 44 tumors as being positive for one of the two mutations. Among the 44 patients with mutation positive tumors, 20 had the same mutation in lymph nodes as in the primary tumors. Furthermore, among the 20 patients with genetically positive lymph nodes, 13 had recurrences within 5 years after surgery, while none of the patients with genetically negative lymph nodes developed recurrence. These data indicate that the rare colorectal cancer cells in blood or lymph nodes, histologically negative for metastasis, are geneticaly detectable. This genetic detection system may be clinically applicable for stratifying patients who are at high versus low risk for recurrence.

Key words
genetic diagnosis, micrometastatsis, colorectal cancer

Reprint requests
Shoji Nakamori The First Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases
1-3-3 Nakamichi, Higashinari, Osaka, 537 JAPAN

Accepted
December 11, 1996

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