对一种实验室研发的用于膀胱癌检测的寡核苷酸荧光原位杂交探针组检测方法进行为期一年的监测。

One-year monitoring of an oligonucleotide fluorescence in situ hybridization probe panel laboratory-developed test for bladder cancer detection.

作者信息

Tinawi-Aljundi Rima, King Lauren, Knuth Shannon T, Gildea Michael, Ng Carrie, Kahl Josh, Dion Jacqueline, Young Chris, Schervish Edward W, Frontera J Rene, Hafron Jason, Kernen Kenneth M, Di Loreto Robert, Aurich-Costa Joan

机构信息

Michigan Institute of Urology, St Claire Shores, MI, USA.

Cellay, Inc., Cambridge, MA, USA.

出版信息

Res Rep Urol. 2015 Apr 9;7:49-55. doi: 10.2147/RRU.S79085. eCollection 2015.

DOI:10.2147/RRU.S79085

PMID:25914883

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4399392/

Abstract

BACKGROUND

Previously, we had developed and manufactured an oligonucleotide fluorescence in situ hybridization (OligoFISH) probe panel based on the most clinically sensitive chromosomes found in a reference set of bladder carcinoma cases. The panel was clinically validated for use as a diagnostic and monitoring assay for bladder cancer, reaching 100% correlation with the results of the UroVysion test. After 1 year of using this probe panel, we present here the comparison of cytology, cystoscopy, and pathology findings to the OligoFISH probe panel results to calculate its clinical performance.

MATERIALS AND METHODS

In order to calculate clinical performance, we compared the OligoFISH results to the cytology and cystoscopy/pathology findings for 147 initial diagnoses and 399 recurrence monitorings. Finally, we compared clinical performance to published values for the UroVysion test, including both low- and high-grade tumors.

RESULTS

Chromosomes 3, 6, 7, and 20 were highly involved in bladder carcinoma aneuploidy. At the initial diagnosis, we obtained 90.5% (95% confidence interval [CI]: 84.5%-94.7%) accuracy, 96.8% sensitivity (95% CI: 91.0%-99.3%), 79.2% specificity (95% CI: 65.9%-87.8%), 89.2% positive predictive value (PPV; 95% CI: 81.5%-94.5%), and 93.3% negative predictive value (NPV; 95% CI: 81.7%-97.3%). When monitoring for recurrence, we obtained 85.2% accuracy (95% CI: 81.3%-88.5%), 82.0% sensitivity (95% CI: 76.0%-87.1%), 88.4% specificity (95% CI: 83.2%-92.5%), 87.7% PPV (95% CI: 82.1%-92.0%), and 83.0% NPV (95% CI: 77.3%-87.8%). When looking at low- and high-grade tumors, the test showed 100% sensitivity for high-grade tumors (95% CI: 92.5%-100%) and 87.5% sensitivity (95% CI: 68.8%-95.5%) for low-grade tumors. All the clinical parameters for the OligoFISH panel were higher than the UroVysion test's published performance. We found significantly higher clinical sensitivity and NPV at initial diagnosis and significantly higher specificity and PPV for recurrence.

CONCLUSION

The OligoFISH probe panel is a fast, easy, and reproducible test for bladder cancer diagnosis and monitoring, with excellent clinical performance and utility.

摘要

背景

此前，我们基于一组膀胱癌病例参考集中发现的临床上最敏感的染色体，开发并制造了一种寡核苷酸荧光原位杂交（OligoFISH）探针组。该探针组经临床验证可作为膀胱癌的诊断和监测检测方法，与UroVysion检测结果的相关性达100%。在使用该探针组1年后，我们在此展示将细胞学、膀胱镜检查和病理结果与OligoFISH探针组结果进行比较，以计算其临床性能。

材料与方法

为了计算临床性能，我们将147例初始诊断和399例复发监测的OligoFISH结果与细胞学和膀胱镜检查/病理结果进行了比较。最后，我们将临床性能与已发表的UroVysion检测值进行了比较，包括低级别和高级别肿瘤。

结果

3号、6号、7号和二十号染色体高度参与膀胱癌非整倍体形成。在初始诊断时，我们获得了90.5%（95%置信区间[CI]：84.5%-94.7%）的准确率、96.8%的灵敏度（9%置信区间：91.0%-99.3%）、79.2%的特异度（95%置信区间：65.9%-87.8%）、89.2%的阳性预测值（PPV；95%置信区间：81.%5%-94.5%）和93.3%的阴性预测值（NPV；95%置信区间：81.7%-97.3%）。在监测复发时，我们获得了85.2%的准确率（95%置信区间：81.3%-88.5%）、%82.0%的灵敏度（95%置信区间：76.0%-87.1%）、88.4%的特异度（95%置信区间：83.2%-92.5%）、87.7%的PPV（95%置信区间：82.1%-92.0%）和83.0%的NPV（95%置信区间：77.3%-87.8%）。在观察低级别和高级别肿瘤时，该检测对高级别肿瘤的灵敏度为100%（95%置信区间：92.5%-100%），对低级别肿瘤的灵敏度为87.5%（95%置信区间：68.8%-95.5%）。OligoFISH探针组的所有临床参数均高于已发表的UroVysion检测性能。我们发现在初始诊断时临床灵敏度和NPV显著更高，在复发时特异度和PPV显著更高。