PMID- 12874783 OWN - NLM STAT- MEDLINE DCOM- 20031031 LR - 20061115 IS - 1045-2257 (Print) IS - 1045-2257 (Linking) VI - 38 IP - 1 DP - 2003 Sep TI - Aneuploidy in oncocytic lesions of the thyroid gland: diffuse accumulation of mitochondria within the cell is associated with trisomy 7 and progressive numerical chromosomal alterations. PG - 22-31 AB - Oncocytic cells are characterized by a greatly increased number of mitochondria that distend the cell cytoplasm and result in a distinctive granular appearance of the cell on conventional histology sections. Oncocytes are frequently found in metabolically active human tissues including the thyroid gland, and, as a general rule, when their proportion in a thyroid tumor is greater than 75% the tumor is referred to as oncocytic (Hurthle cell) adenoma or carcinoma. Such tumors represent a subset of thyroid lesions, and recently, both interphase fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) studies reported that they may show aneuploidy, with widespread numerical chromosomal alterations. In contrast, very few cases have been studied by conventional cytogenetic analysis. Whether the cells with chromosomal changes are the same as those with mitochondrial accumulation or whether lesions only partially composed of oncocytic cells also have cytogenetic alterations is unclear. To investigate the relationship between acquisition of the oncocytic phenotype and numerical chromosomal changes, we analyzed a random selection of thyroid lesions with (18 cases) and without (11 cases) morphological evidence of oncocytic differentiation. Lesions with oncocytes included hyperplastic nodules, adenomas, Hurthle cell tumors, and papillary carcinomas with lymphocytic stroma (Whartin-like tumors of the thyroid). Karyotypic changes were analyzed by cytogenetic analysis, FISH, or CGH, and the results were compared with in situ analysis of mitochondrial accumulation by immunofluorescence. A striking correlation between the presence of oncocytes and the presence of aneuploid katyotypes was seen in the oncocytic follicular thyroid nodules, but not in the oncocytic papillary tumors. Structural chromosome changes or normal karyotypes were observed in the lesions lacking oncocytic features. Extending the FICTION technique to the evaluation of a cytoplasmic antigen (mitochondrial membrane antigen), we pursued the simultaneous visualization of both mitochondrial increase and numerical chromosomal alterations, and showed that oncocytes of follicular lesions are prone to become aneuploid. Our data support the contention that follicular tumors composed of oncocytes should be regarded as a distinct subset. CI - Copyright 2003 Wiley-Liss, Inc. FAU - Dettori, Tinuccia AU - Dettori T AD - Department of Biomedical Sciences and Technology, University of Cagliari, Cagliari, Italy. FAU - Frau, Daniela V AU - Frau DV FAU - Lai, Maria L AU - Lai ML FAU - Mariotti, Stefano AU - Mariotti S FAU - Uccheddu, Alessandro AU - Uccheddu A FAU - Daniele, Giovanni M AU - Daniele GM FAU - Tallini, Giovanni AU - Tallini G FAU - Faa, Gavino AU - Faa G FAU - Vanni, Roberta AU - Vanni R LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Genes Chromosomes Cancer JT - Genes, chromosomes & cancer JID - 9007329 SB - IM MH - Adolescent MH - Adult MH - Aged MH - *Aneuploidy MH - Chromosome Disorders/*genetics MH - Chromosomes, Human, Pair 7/*genetics MH - Cytogenetic Analysis/methods MH - Female MH - Fluorescent Antibody Technique, Indirect MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Male MH - Middle Aged MH - Mitochondria/*genetics/metabolism/pathology MH - Nucleic Acid Hybridization/methods MH - Oxyphil Cells/metabolism/*pathology MH - Thyroid Neoplasms/*genetics/metabolism MH - Trisomy/*genetics EDAT- 2003/07/23 05:00 MHDA- 2003/11/01 05:00 CRDT- 2003/07/23 05:00 PHST- 2003/07/23 05:00 [pubmed] PHST- 2003/11/01 05:00 [medline] PHST- 2003/07/23 05:00 [entrez] AID - 10.1002/gcc.10238 [doi] PST - ppublish SO - Genes Chromosomes Cancer. 2003 Sep;38(1):22-31. doi: 10.1002/gcc.10238.