Correspondence

Tumorigenic Potential of Apparently Tumor-Free Lymph Nodes

N Engl J Med 1999; 340:1687May 27, 1999

Article

To the Editor:

Metastatic relapse after the complete resection of an apparently localized primary tumor indicates that disseminated cancer cells, present at the time of surgery, are sometimes undetectable by current methods. Using monoclonal antibody Ber-Ep4 against an epithelial-cell surface antigen, we can detect one tumor cell in a background of 10⁴ to 10⁵ lymph-node cells. This finding is prognostically relevant in patients with operable lung or esophageal cancer.1,2 However, it remains unclear whether these immunopositive cells are viable tumor cells with metastatic potential, shed tumor cells with a limited life span, or simply laboratory artifacts.3

We report direct evidence that immunohistochemical analysis can identify viable tumor cells with tumorigenic potential. With the use of culture methods,4 a unique cell line (LN1590) was generated from a lymph node obtained from a patient with esophageal cancer classified as stage pT₁pN₁M₀, according to the tumor–node–metastasis classification of the International Union against Cancer. The node was classified as tumor-free by routine pathological methods (hematoxylin and eosin staining), but it contained 3 Ber-Ep4–positive cells per approximately 10⁵ lymph-node cells (Figure 1AFigure 1Cryostat Section of a Left-Sided Gastric-Artery Lymph Node with a Red-Stained, Isolated Ber-Ep4–Positive Tumor Cell (Panel A), and Local Tumor Formation after Subcutaneous Injection of LN1590 Cells into a Mouse with Severe Combined Immunodeficiency (Panel B).). The cultured cells were transplanted subcutaneously into seven mice with severe combined immunodeficiency. Progressive tumor nodules were observed in all seven animals (Figure 1B).

This result proves that the cultured cells indeed contained malignant tumor cells. Moreover, cytogenetic changes found in the lymph-node tumor cells with the use of a novel cytogenetic technique termed multiplex fluorescence in situ hybridization5 directly support the concept of selection during the process of lymphatic dissemination (Kraus J, Speicher M, University of Munich: personal communication).

Our observation should have important consequences for tumor staging. If immunohistochemically identifiable cells in lymph nodes represent viable tumor cells, this information should be incorporated into the staging nomenclature of the International Union against Cancer.

Peter Scheunemann, M.D.
Jakob Robert Izbicki, M.D.
Klaus Pantel, M.D.
Universitätsklinikum Eppendorf, D-20246 Hamburg, Germany

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Citing Articles (21)

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