Correspondence

Cryptic Tumor Cells in Lymph Nodes of Patients with Esophageal Cancer

N Engl J Med 1998; 338:550-551February 19, 1998

Article

To the Editor:

Perhaps the study by Izbicki et al. (Oct. 23 issue)1 on immunohistochemical identification of tumor deposits in lymph nodes from patients with esophageal cancer is of value, but since I can't interpret the published photomicrographs I can't believe their results. Even the legend and arrow in Panel A of their Figure 1 aren't enough to convince me that a tumor cell is shown. If this is what the authors chose for publication — ambiguous staining in a section that may be technically inferior (the tissue appears shredded) — I have to wonder what they were attempting to interpret most of the time, and I have to doubt their analyses.

Why was the study designed to require cryostat sections, when the antibody used is said (in the reference the authors cite 2) to work in formalin-fixed, paraffin-embedded material? That seems to stack the deck against the pathologist.

A.S. Knisely, M.D.
Denver–Aurora Pathology Associates, Denver, CO 80218

2 References

1. 1

   Izbicki JR, Hosch SB, Pichlmeier U, et al. Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer. N Engl J Med 1997;337:1188-1194
   Full Text | Web of Science | Medline

2. 2

   Passlick B, Izbicki JR, Kubuschok B, et al. Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer. J Clin Oncol 1994;12:1827-1832
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree with Knisely that formalin-fixed, paraffin-embedded material would have allowed a better morphologic evaluation of the lymph-node sections. However, formalin fixation has the disadvantage of potentially destroying Ber-EP4 antigens, which might reduce the sensitivity and reproducibility of our assay. Moreover, it is sometimes impossible to distinguish the suspicious cell from autochthonous epithelioid reticulum cells in formalin-fixed, paraffin-embedded lymph nodes.1 We therefore defined the specificity of our assay by the consistent absence of Ber-EP4 immunostaining in lymph nodes from control patients without carcinoma. We also searched for additional proof that the identified cells are tumor cells. Using culture conditions previously established for in vitro expansion of micrometastatic carcinoma cells,2 we could generate a permanent cell line from a lymph node that was classified as tumor-free in routine staining with hematoxylin and eosin but showed a Ber-EP4–positive cell. This cell line showed characteristic features of epithelial tumor cells, such as expression of Lewis Y antigen, 67-kD laminin receptor, erbB-2 oncogene, and loss of major histocompatibility complex class I antigen. Moreover, it is tumorigenic and metastatic after xenotransplantation into immunodeficient SCID (severe combined immunodeficiency) mice. Taken together, these findings clearly show that viable tumor cells are present in histopathologically negative but Ber-EP4–positive lymph nodes of patients with esophageal cancer.

Stefan B. Hosch, M.D.
Universität Hamburg, D-20246 Hamburg, Germany

Klaus Pantel, M.D.
Ludwig-Maximilians-Universität, D-80336 Munich, Germany

Jakob R . Izbicki, M.D.
Universität Hamburg, D-20246 Hamburg, Germany

2 References

1. 1

   Passlick B, Izbicki JR, Kubuschok B, et al. Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer. J Clin Oncol 1994;12:1827-1832
   Web of Science | Medline

2. 2

   Pantel K, Dickmanns A, Zippelius A, et al. Establishment of micrometastatic carcinoma cell lines: a novel source of tumor cell vaccines. J Natl Cancer Inst 1995;87:1162-1168
   CrossRef | Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   Alexandra M. Koenig, Klaus L. Prenzel, Dean Bogoevski, Emre F. Yekebas, Michael Bubenheim, Lucia Faithova, Yogesh K. Vashist, Karim A. Gawad, Stephan E. Baldus, Klaus Pantel, Paul M. Schneider, Arnulf H. Hölscher, Jakob R. Izbicki. (2009) Strong Impact of Micrometastatic Tumor Cell Load in Patients with Esophageal Carcinoma. Annals of Surgical Oncology 16:2, 454-462
   CrossRef

2. 2

   C. Milsmann, L. Füzesi, E. Heinmöller, P. Krause, C. Werner, H. Becker, O. Horstmann. (2007) Morphological and immunohistochemical characterization of isolated tumor cells by p53 status in gastrointestinal tumors. Langenbeck's Archives of Surgery 393:1, 49-58
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3. 3

   P. Scheuemann, S. B. Hosch, J. R. Izbicki. (2001) Cytokeratins and other sensitive markers for esophageal cancer and metastases*. Diseases of the Esophagus 14:2, 85-90
   CrossRef

4. 4

   Scheunemann, Peter, Izbicki, Jakob Robert, Pantel, Klaus, . (1999) Tumorigenic Potential of Apparently Tumor-Free Lymph Nodes. New England Journal of Medicine 340:21, 1687-1687
   Full Text