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Papillary and Follicular Thyroid Carcinomas Show Distinctly Different Microarray Expression Profiles and Can Be Distinguished by a Minimum of Five Genes

From the Human Cancer Genetics Program; Clinical Cancer Genetics Program; Comprehensive Cancer Center; Division of Human Cancer Genetics, Department of Molecular Virology, Immunology, and Medical Genetics; Division of Human Genetics, Department of Internal Medicine; and Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH; Department of Surgery, Martin-Luther-University, Halle-Wittenberg, Halle/Saale, Germany; Division of Medical Genetics, University of Leicester, Leicester; and Cancer Research United Kingdom Human Cancer Genetics Research Group, University of Cambridge, Cambridge, United Kingdom

Address reprint requests to Charis Eng, MD, PhD, Human Cancer Genetics Program, The Ohio State University, 420 W 12th Ave, Suite 690 TMRF, Columbus, OH 43210; e-mail: eng-1{at}medctr.osu.edu

PURPOSE: We have previously conducted independent microarray expression analyses of the two most common types of nonmedullary thyroid carcinoma, namely papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). In this study, we sought to combine our data sets to shed light on the similarities and differences between these tumor types.

MATERIALS AND METHODS: Microarray data from six PTCs, nine FTCs, and 13 normal thyroid samples were normalized to remove interlaboratory variability and then analyzed by unsupervised clustering, t test, and by comparison of absolute and change calls. Expression changes in four genes not previously implicated in thyroid carcinogenesis were verified by reverse transcriptase polymerase chain reaction on these same samples, together with eight additional FTC tumors.

RESULTS: PTCs showed two distinct groups of genes that were either over- or underexpressed compared with normal thyroid, whereas the predominant changes in FTCs were of decreased expression. Five genes could collectively distinguish the two tumor types. PTCs showed overexpression of CITED1, claudin-10 (CLDN10), and insulin-like growth factor binding protein 6 (IGFBP6) but showed no change in expression of caveolin-1 (CAV1) or -2 (CAV2); conversely, FTCs did not express CLDN10 and had decreased expression of IGFBP6 and/or CAV1 and CAV2.

CONCLUSION: PTC and FTC show distinctive microarray expression profiles, suggesting that either they have different molecular origins or they diverge distinctly from a common origin. Furthermore, if verified in a larger series of tumors, these genes could, in combination with known tumor-specific chromosome translocations, form the basis of a valuable diagnostic tool.

Supported by an Advanced Training Fellowship from the Wellcome Trust (M.A.A.; ref: 064271/Z/01/Z). C.E. is a recipient of the Doris Duke Distinguished Clinical Scientist Award. This work was partially funded by National Cancer Institute grant No. P30CA16058 to The Ohio State University Comprehensive Cancer Center, and by a generous gift from the Brown family in memory of Welton D. Brown (C.E.).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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