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Molecular Profiling of Matched Samples Identifies Biomarkers of Papillary Thyroid Carcinoma Lymph Node Metastasis

¹ Department of Neurosurgery, Johns Hopkins University Medical School, Baltimore, Maryland; ² Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, ³ Department of Pathology, Federal University of São Paulo, and ⁴ Division of Head and Neck Surgery, Department of Surgery, University of São Paulo Medical School, São Paulo, SP, Brazil; and ⁵ Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina

Requests for reprints: Janete Cerutti, Rua Pedro de Toledo 781, 12° andar., Federal University of São Paulo, 04039-032, São Paulo, SP, Brazil. Phone: 55-11-5081-5233; Fax: 55-11-5084-5231; E-mail: cerutti-endo{at}pesquisa.epm.br.

Biomarkers of papillary thyroid carcinoma (PTC) metastasis can accurately identify metastatic cells and aggressive tumor behavior. To find new markers, serial analysis of gene expression (SAGE) was done on three samples from the same patient: normal thyroid tissue, primary PTC, and a PTC lymph node metastasis. This genomewide expression analysis identified 31 genes expressed in lymph node metastasis, but not in the primary tumor. Eleven genes were evaluated by quantitative real-time reverse transcription-PCR (qPCR) on independent sets of matched samples to find genes that were consistently different between the tumor and metastatic samples. LIMD2 and PTPRC (CD45) showed a statistically significant difference in expression between tumor and metastatic samples (P < 0.0045), and an additional gene (LTB) had borderline significance. PTPRC and LTB were tested by immunohistochemistry in an independent set of paired samples, with both markers showing a difference in protein expression. All 20 metastases from 6 patients showed expression in both markers, with little or no expression in primary tumor. Some of these markers could provide an improved means to detect metastatic PTC cells during initial staging of a newly diagnosed carcinoma and/or to rule out recurrence. The functional role of these genes may also provide insight into mechanisms of thyroid cancer metastasis. [Cancer Res 2007;67(16):7885–92]

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