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Original Article
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Volume 337:1188-1194 October 23, 1997 Number 17
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Prognostic Value of Immunohistochemically Identifiable Tumor Cells in Lymph Nodes of Patients with Completely Resected Esophageal Cancer
Jakob Robert Izbicki, M.D., Stefan Benedikt Hosch, M.D., Uwe Pichlmeier, Ph.D., Alexander Rehders, Christoph Busch, M.D., Axel Niendorf, M.D., Bernward Passlick, M.D., Christoph Erich Broelsch, M.D., and Klaus Pantel, M.D.

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ABSTRACT

Background Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells.

Methods We studied 1308 lymph nodes from 68 patients with esophageal cancer without overt metastases who had undergone radical en bloc esophagectomy. A total of 399 lymph nodes obtained from 68 patients were found to be free of tumor by routine histopathological analysis and were studied further for isolated tumor cells by immunohistochemical analysis with the monoclonal anti–epithelial-cell antibody Ber-EP4. This antibody did not stain lymph nodes from 24 control patients without carcinoma.

Results Of the 399 "tumor free" lymph nodes, 67 (17 percent), obtained from 42 of the 68 patients, contained Ber-EP4–positive tumor cells. Fifteen of 30 patients who were considered free of lymph-node metastases by histopathological analysis had such cells in their lymph nodes, and 5 of the 15 had small primary tumors. Ber-EP4–positive cells found in "tumor free" nodes were independently predictive of significantly reduced relapse-free survival (P = 0.008) and overall survival (P = 0.03). They predicted relapse both in patients without nodal metastases (P = 0.01) and in those with regional lymph-node involvement (P = 0.007). All 12 patients whose lymph nodes were negative on both histopathological and immunohistochemical analysis and who were available for follow-up survived without recurrence. The presence of micrometastatic tumor cells in bone marrow had no additional prognostic value.

Conclusions Immunohistochemical examination of lymph nodes may improve the pathological staging of esophageal cancer.


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From the Abteilung f ür Allgemeinchirurgie, Universitätskrankenhaus Eppendorf (J.R.I., S.B.H., A.R., C.B., B.P., C.E.B.), the Abteilung f ür Mathematik in der Medizin (U.P.), and the Institut für Pathologie (A.N.), Universität Hamburg, Hamburg; and the Institut für Immunologie, Ludwig-Maximilians-Universität, Munich (K.P.) — all in Germany.

Address reprint requests to Dr. Izbicki at the Abt. für Allgemeinchirurgie, Universitätskrankenhaus Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.

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Related Letters:

Cryptic Tumor Cells in Lymph Nodes of Patients with Esophageal Cancer
Knisely A.S., Hosch S. B., Pantel K., Izbicki J. R .
Extract | Full Text  
N Engl J Med 1998; 338:550-551, Feb 19, 1998. Correspondence

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