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.
Background Current methods of disease staging often fail todetect small numbers of tumor cells in lymph nodes. Metastaticrelapse may arise from these few cells.
Methods We studied 1308 lymph nodes from 68 patients with esophagealcancer without overt metastases who had undergone radical enbloc esophagectomy. A total of 399 lymph nodes obtained from68 patients were found to be free of tumor by routine histopathologicalanalysis and were studied further for isolated tumor cells byimmunohistochemical analysis with the monoclonal antiepithelial-cellantibody Ber-EP4. This antibody did not stain lymph nodes from24 control patients without carcinoma.
Results Of the 399 "tumor free" lymph nodes, 67 (17 percent),obtained from 42 of the 68 patients, contained Ber-EP4positivetumor cells. Fifteen of 30 patients who were considered freeof lymph-node metastases by histopathological analysis had suchcells in their lymph nodes, and 5 of the 15 had small primarytumors. Ber-EP4positive cells found in "tumor free" nodeswere independently predictive of significantly reduced relapse-freesurvival (P = 0.008) and overall survival (P = 0.03). They predictedrelapse 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 histopathologicaland immunohistochemical analysis and who were available forfollow-up survived without recurrence. The presence of micrometastatictumor cells in bone marrow had no additional prognostic value.
Conclusions Immunohistochemical examination of lymph nodes mayimprove the pathological staging of esophageal cancer.
Source Information
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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