have also identified chromosomal aberrations in papillary, follicular, medullary, and ... CGH in Hü rthle cell carcinomas would correlate with tumor stage and ...
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The Journal of Clinical Endocrinology & Metabolism 87(10):4595– 4601 Copyright © 2002 by The Endocrine Society doi: 10.1210/jc.2002-020339
Chromosomal Aberrations by Comparative Genomic Hybridization in Hu ¨ rthle Cell Thyroid Carcinomas Are Associated with Tumor Recurrence NOBUYUKI WADA, QUAN-YANG DUH, DAISHU MIURA, LAURENT BRUNAUD, MARIWIL G. WONG, AND ORLO H. CLARK Endocrine Surgical Oncology Fellows (N.W., D.M., L.B.), Department of Surgery, University of California, San Francisco, and UCSF/Mount Zion Medical Center (M.G.W., O.H.C.), San Francisco, California 94143; Surgical Service, Veterans Affairs Medical Center (Q.-Y.D.), San Francisco, California 94121; First Department of Surgery (N.W.), Yokohama City University School of Medicine, Yokohama 236-0004, Japan; and Department of Endocrine Surgery (D.M.), Toranomon Hospital, Tokyo 105-8470, Japan Hu ¨ rthle cell thyroid neoplasms are classified as variants of follicular neoplasms, but they have distinct clinicopathological features. Chromosomal aberrations by comparative genomic hybridization (CGH) are common in Hu ¨ rthle cell neoplasms. However, there is currently only limited information concerning the relationship between the chromosomal aberrations by CGH and tumor behavior. We, therefore, investigated chromosomal aberrations in primary Hu ¨ rthle cell neoplasms (13 carcinomas and 15 adenomas) using CGH and correlated the aberrations identified with tumor node metastasis (TNM) stage, tumor differentiation, capsular invasion, and tumor recurrence. Chromosomal aberrations were found in 62% (8 of 13) of carcinomas and 60% (9 of 15) of adenomas. Overall, common chromosomal gains were found on 5p (29%), 5q (36%), 7 (29%), 12p (14%), 12q (21%), 17p (29%), 17q (32%), 19p (32%), 19q (25%), 20p (21%), 20q (29%), and 22q (18%). Common chromosomal losses were found on 2q (18%) and 9q (18%).
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¨ RTHLE CELL CARCINOMA of the thyroid accounts U for approximately 3% of all thyroid cancers. Although Hu¨rthle cell carcinomas are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than other follicular neoplasms (1– 6). Some authors consider that all Hu¨rthle cell neoplasms are malignant and should be treated accordingly (7, 8). Most authors, however, suggest that Hu¨rthle cell neoplasms can be separated into benign (no capsular and vascular invasion) or malignant using similar criteria as used for follicular neoplasms (1–3, 9) and also suggest that Hu¨rthle cell carcinomas do not necessarily carry an unfavorable clinical outcome (6, 10). Genetic alterations in Hu¨rthle cell neoplasms have been studied by various techniques, including DNA ploidy (11– 14), cytogenetic (karyotype), and fluorescence in situ hybridization (FISH; Refs. 15–17), and most recently by comparative genomic hybridization (CGH; Refs. 18 –20). CGH studies have also identified chromosomal aberrations in papillary, follicular, medullary, and anaplastic thyroid carcinomas (18, 19, 21–28). CGH enables the analysis of the entire genome for Abbreviations: CGH, Comparative genomic hybridization; dUTP, deoxyuracil triphosphate; FISH, fluorescence in situ hybridization; TNM, tumor node metastasis.
Thirty-eight percent (5 of 13) of carcinomas were TNM stage III, 31% (4 of 13) were moderately to poorly differentiated, and 46% (6 of 13) were intermediately to widely invasive. Recurrence occurred in 38% (5 of 13). Carcinomas that subsequently recurred had a greater number of chromosomal gains (9.0 vs. 1.3;
