This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation

Loss of Heterozygosity of the Long Arm of Chromosome 7 in Follicular and Anaplastic Thyroid Cancer, but Not in Papillary Thyroid Cancer¹

Dipartimento di Patologia Umana (M.T., D.V., D.B.), Policlinico Universitario, 98125 Messina, Italy; Anatomia Patologica (F.F.), Università degli Studi di Catania, 95124 Catania, Italy; Molecular Research Center, Inc. (K.M.), Cincinnati, Ohio 45212; Cattedra di Endocrinologia (F.T., S.B.), Policlinico Universitario, 98125 Messina, Italy

Address all correspondence and requests for reprints to: Maria Trovato, Dipartimento di Patologia Umana, Padiglione D, Policlinico Universitario, Gazzi - 98125 Messina, Italy.

Papillary thyroid cancer (PTC), but neither the follicular nor the anaplastic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at multiple loci with a frequency much higher than PTC, and 3) loss of heterozygosity (LOH) on 7q has been previously found in various tumors, we tested the hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segments of 7q encompassing the loci for HGF and c-met.

We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasias, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 PTC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 markers) in 10–29% of FA.

This is the first demonstration of an LOH that separates both FTC and ATC from PTC, in the best possible manner: 100% vs. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC (and ATC) phenotype. This loss of genetic material explains why FTC and ATC, but not PTC, fail to express both HGF and c-met. Our findings may also have immediate diagnostic application, in the context of assisting pathologists in the often difficult task of distinguishing FA from FTC.

This article has been cited by other articles:

				M. Sunde, K. C. Y. McGrath, L. Young, J. M. Matthews, E. L. Chua, J. P. Mackay, and A. K. Death TC-1 Is a Novel Tumorigenic and Natively Disordered Protein Associated with Thyroid Cancer Cancer Res., April 15, 2004; 64(8): 2766 - 2773. [Abstract] [Full Text] [PDF]

				H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass Angiogenesis in Endocrine Tumors Endocr. Rev., October 1, 2003; 24(5): 600 - 632. [Abstract] [Full Text] [PDF]

				M. A. Aldred, M. E. Ginn-Pease, C. D. Morrison, A. P. Popkie, O. Gimm, C. Hoang-Vu, U. Krause, H. Dralle, S. M. Jhiang, C. Plass, et al. Caveolin-1 and Caveolin-2,Together with Three Bone Morphogenetic Protein-related Genes, May Encode Novel Tumor Suppressors Down-Regulated in Sporadic Follicular Thyroid Carcinogenesis Cancer Res., June 1, 2003; 63(11): 2864 - 2871. [Abstract] [Full Text] [PDF]

				Y. Kitamura, K. Shimizu, K. Ito, S. Tanaka, and M. Emi Allelotyping of Follicular Thyroid Carcinoma: Frequent Allelic Losses in Chromosome Arms 7q, 11p, and 22q J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4268 - 4272. [Abstract] [Full Text] [PDF]