Wehle Danielle, Yonescu Raluca, Long Patricia P, Gala Nalini, Epstein Jonathan, Griffin Constance A
Department of Pathology and Laboratory Medicine, The Johns Hopkins University, 600 North Wolfe Street, Park Building SB202, Baltimore, MD 21287.
Cancer Genet Cytogenet. 2008 Jun;183(2):99-104. doi: 10.1016/j.cancergencyto.2008.02.012.
Most germ cell tumors have an isochromosome 12p (detected by metaphase cytogenetics), 12p overrepresentation (detected by fluorescence in situ hybridization [FISH]), or both. Although interphase FISH on paraffin-embedded tissue is a sensitive method of detection of 12p anomalies, use of FISH for clinical diagnostic purposes is not well defined. We describe an interphase FISH assay for detection of increased 12p copy number in germ cell tumors using a bacterial artificial chromosome-derived probe localized to 12p12.1 and a commercially available probe for the centromere of chromosome 12. Twenty-four paraffin-embedded blocks from 14 tumor cases (7 malignant mixed germ cell tumors, 2 dysgerminomas, 4 non-germ cell malignancies arising in germ cell tumors, and 1 mediastinal adenocarcinoma) and 18 normal controls were studied. Negative controls included normal lymph node, lung, and mediastinal tissue. The signals for 12p and 12cen were counted, and the ratio of the averaged signals was calculated; a ratio of 1.3 was considered positive. All germ cell tumors and non-germ cell malignancies arising in germ cell tumors were positive for 12p overrepresentation. All control cases were negative. Because germ cell tumors may metastasize with non-germ cell tumor morphology, interphase FISH may be helpful in distinguishing de novo malignancy from germ cell tumor recurrence in its various forms.
大多数生殖细胞肿瘤具有12号染色体短臂等臂染色体（通过中期细胞遗传学检测）、12号染色体短臂过度表达（通过荧光原位杂交[FISH]检测），或两者兼具。虽然对石蜡包埋组织进行间期FISH是检测12号染色体短臂异常的一种敏感方法，但FISH用于临床诊断目的的应用尚未明确界定。我们描述了一种间期FISH检测方法，使用定位于12p12.1的细菌人工染色体衍生探针和市售的12号染色体着丝粒探针，检测生殖细胞肿瘤中12号染色体短臂拷贝数增加。研究了来自14例肿瘤病例（7例恶性混合性生殖细胞肿瘤、2例无性细胞瘤、4例起源于生殖细胞肿瘤的非生殖细胞恶性肿瘤和1例纵隔腺癌）的24个石蜡包埋块以及18个正常对照。阴性对照包括正常淋巴结、肺和纵隔组织。对12号染色体短臂和12号染色体着丝粒的信号进行计数，并计算平均信号的比值；比值为1.3被视为阳性。所有生殖细胞肿瘤以及起源于生殖细胞肿瘤的非生殖细胞恶性肿瘤均显示12号染色体短臂过度表达阳性。所有对照病例均为阴性。由于生殖细胞肿瘤可能以非生殖细胞肿瘤形态发生转移，间期FISH可能有助于区分新发恶性肿瘤与各种形式的生殖细胞肿瘤复发。
