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Detection of Melanoma Cells Displaying Multiple Genomic Changes in Histopathologically Negative Sentinel Lymph Nodes

Authors' Affiliations: ¹ Universitäts-Hautklinik, Eberhard-Karls-Universität, Tübingen, Germany ² Institut für Immunologie, Ludwig-Maximilians-Universität, Munich, Germany ³ Institut für Pathologie, Eberhard-Karls-Universität, Tübingen, Germany and ⁴ Institut für Medizinische Biometrie, Eberhard-Karls-Universität, Tübingen, Germany

Requests for reprints: Christoph Klein, Institut für Immunologie, Goethestr. 31, 80336 München, Germany. Phone: 89-5996-696; Fax: 011-49-89-5996-696; E-mail: christopher.klein{at}med.uni-muenchen.de.

Purpose: Improved detection of early-disseminated melanoma cells may eventually translate into more effective patient care. We present a novel strategy for detection of melanoma cells in sentinel lymph nodes and confirm their malignant descent by genomic characterization.

Experimental Design: In sentinel lymph nodes from 358 melanoma patients, we prospectively compared the rates of tumor cell detection between immunocytochemistry using HMB45 and Melan A antibodies on disaggregated lymph node samples and standard histopathology (H&E staining and immunostaining on tissue sections). Immunocytochemical melanoma cell detection was controlled by testing lymph node samples from 59 nonmelanoma patients and by isolation and comparative genomic analysis of 30 antigen-positive cells.

Results: Of the 358 patients, 43 (12%) were positive by standard histopathology, whereas HMB45 immunocytochemistry detected 159 of 358 (44%) positive patients. None of the control samples reacted with the HMB45 antibody. Reexamination of samples that were classified as negative by histopathology revealed that extensive serial sectioning would be necessary to achieve sensitivity similar to HMB45 immunocytochemistry. Interestingly, both the number of immunocytochemically positive samples and the number of positive cells in the sentinel node correlated with the thickness of the primary tumor (r = 0.34; P = 0.001 and P < 0.0001, respectively). Twenty-four of 30 isolated immunocytochemically positive cells (80%) displayed chromosomal aberrations, some of which were isolated from histopathologically negative nodes.

Conclusion: Immunocytochemical detection of melanoma cells in sentinel lymph nodes is superior to standard histopathology. It remains to be determined whether the detection and genomic characterization of isolated melanoma cells in sentinel lymph nodes will provide relevant prognostic information.

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