Dettori Tinuccia, Frau Daniela V, Lai Maria L, Mariotti Stefano, Uccheddu Alessandro, Daniele Giovanni M, Tallini Giovanni, Faa Gavino, Vanni Roberta
Department of Biomedical Sciences and Technology, University of Cagliari, Cagliari, Italy.
Genes Chromosomes Cancer. 2003 Sep;38(1):22-31. doi: 10.1002/gcc.10238.
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 (Hürthle 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, Hürthle 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.
嗜酸性细胞的特征是线粒体数量大幅增加，这些线粒体使细胞质扩张，导致在传统组织学切片上细胞呈现出独特的颗粒状外观。嗜酸性细胞常见于包括甲状腺在内的代谢活跃的人体组织中，一般来说，当它们在甲状腺肿瘤中的比例大于75%时，该肿瘤被称为嗜酸性（许特耳细胞）腺瘤或癌。这类肿瘤是甲状腺病变的一个子集，最近，间期荧光原位杂交（FISH）和比较基因组杂交（CGH）研究均报告称，它们可能显示非整倍体，伴有广泛的染色体数目改变。相比之下，通过传统细胞遗传学分析研究的病例极少。具有染色体变化的细胞是否与线粒体积累的细胞相同，或者仅部分由嗜酸性细胞组成的病变是否也存在细胞遗传学改变尚不清楚。为了研究嗜酸性表型的获得与染色体数目变化之间的关系，我们随机选取了有（18例）和无（11例）嗜酸性分化形态学证据的甲状腺病变进行分析。含有嗜酸性细胞的病变包括增生性结节、腺瘤、许特耳细胞瘤以及伴有淋巴细胞间质的乳头状癌（甲状腺沃辛样肿瘤）。通过细胞遗传学分析、FISH或CGH分析核型变化，并将结果与免疫荧光法对线粒体积累的原位分析进行比较。在嗜酸性滤泡性甲状腺结节中，可见嗜酸性细胞的存在与非整倍体核型的存在之间存在显著相关性，但在嗜酸性乳头状肿瘤中未观察到这种相关性。在缺乏嗜酸性特征的病变中观察到染色体结构变化或正常核型。将FICTION技术扩展用于评估细胞质抗原（线粒体膜抗原），我们实现了线粒体增加和染色体数目改变的同时可视化，并表明滤泡性病变的嗜酸性细胞易于变为非整倍体。我们的数据支持以下观点，即由嗜酸性细胞组成的滤泡性肿瘤应被视为一个独特的子集。
