Scheie David, Andresen Per Arne, Cvancarova Milada, Bø Anne Signe, Helseth Eirik, Skullerud Kari, Beiske Klaus
The Pathology Clinic, Department of Pathology, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway.
Am J Surg Pathol. 2006 Jul;30(7):828-37. doi: 10.1097/01.pas.0000213250.44822.2e.
Combined loss of heterozygosity (LOH) on 1p and 19q is reported in 50% to 90% of oligodendroglial tumors and has emerged as a strong and favorable prognostic factor. Fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are the most widely used techniques. The aim of this study was to evaluate the reliability of FISH to predict LOH at 1p and 19q when performed on touch preparations from 40 oligodendroglial tumors, even if the majority of the nuclei showed chromosomal imbalance. PCR was used as the gold standard. The presence of none or one target signal was reported as FISH-LOH, whereas all other losses were defined as FISH-imbalance. The sum of nuclei with FISH-LOH and imbalance was calculated in each case (FISH-sum) and cut-off values were defined as the mean FISH-sum value in controls plus 3 standard deviations; 27.7% for 1p and 33.2% for 19q. These corresponded well with the optimal cut-off values for our data, calculated using the minimum error rate classification procedure (35.6% for 1p and 33.1% for 19q). Concurrent FISH and PCR results were encountered in 95% for 1p and 87.5% for 19q. FISH-sum was the best and simplest discriminating variable for correct classification of LOH status. Under these conditions, even a dominant population of nuclei showing FISH-imbalance represented an LOH status in the tumor cells. FISH on touch preparations is a quick and reliable method for 1p/19q testing, does not require normal DNA and can be easily performed in an immunohistochemistry unit.
据报道,50%至90%的少突胶质细胞瘤存在1p和19q杂合性缺失(LOH),并且这已成为一个强有力的良好预后因素。荧光原位杂交(FISH)和聚合酶链反应(PCR)是最广泛使用的技术。本研究的目的是评估对40例少突胶质细胞瘤的触摸涂片进行FISH检测以预测1p和19q处LOH的可靠性,即便大多数细胞核显示出染色体失衡。PCR被用作金标准。无靶信号或仅有一个靶信号存在被报告为FISH-LOH,而所有其他缺失被定义为FISH失衡。计算每种情况下具有FISH-LOH和失衡的细胞核总数(FISH总数),并将临界值定义为对照组中FISH总数的平均值加上3个标准差;1p为27.7%,19q为33.2%。这些与使用最小错误率分类程序计算出的我们数据的最佳临界值非常吻合(1p为35.6%,19q为33.1%)。1p的FISH和PCR结果一致性为95%,19q为87.5%。FISH总数是正确分类LOH状态的最佳且最简单的判别变量。在这些条件下,即使大多数显示FISH失衡的细胞核群体也代表肿瘤细胞中的LOH状态。对触摸涂片进行FISH检测是一种快速且可靠的1p/19q检测方法,不需要正常DNA,并且可以在免疫组织化学单元轻松进行。