荧光原位杂交与尿脱落细胞学在尿路上皮癌诊断中的效能比较：一项单中心回顾性队列研究

doi:10.19401/j.cnki.1007-3639.2024.12.002

摘要/Abstract

摘要：

背景与目的：尿路上皮癌是泌尿系统常见的恶性肿瘤，其早期诊断对改善患者预后至关重要。本研究比较了荧光原位杂交（fluorescence in situ hybridization，FISH）、尿脱落细胞学及二者联合检测在尿路上皮癌及其不同亚型中的诊断效能。方法：本研究纳入了2022年1月—2023年12月行经尿道膀胱肿瘤切除术（transurethral resection of bladder tumor，TURBT）且符合入组标准及排除标准的患者，且获得复旦大学附属肿瘤医院伦理委员会批准（伦理批号：050432-4-2307E）。收集患者本次TURBT后病理学诊断结果及术前1周的FISH和脱落细胞学检测结果，对FISH、脱落细胞学及二者联合检测在尿路上皮癌中的诊断准确率、灵敏度和特异度进行统计学分析。本研究属于观察性研究，严格遵循《加强流行病学中观察性研究报告质量》（Strengthening the Reporting of Observational Studies in Epidemiology，STROBE）指南及《诊断准确性研究报告规范》（Standards for Reporting of Diagnostic Accuracy，STARD）中的各项条目。结果：本研究共纳入283例TURBT术后患者，其中136例为尿路上皮癌，147例为良性病变。136例尿路上皮癌中，根据病理学亚型分组，79（58.09%）例为浸润性尿路上皮癌，57（41.91%）例为非浸润性尿路上皮癌。根据恶性程度分组，112（82.35%）例为高级别尿路上皮癌，24（17.65%）例为低级别尿路上皮癌。以组织病理学诊断结果为金标准，136例尿路上皮癌中FISH、脱落细胞学、联合检测的准确率分别为79.51%、72.08%、77.39%，灵敏度分别为72.06%、58.82%、78.68%，特异度分别为86.39%、84.35%、76.19%。FISH、联合检测的曲线下面积（area under the curve，AUC）差异无统计学意义，但均高于脱落细胞学（0.792 vs 0.716，P=0.006;0.774 vs 0.716，P=0.004）;FISH与脱落细胞学相比，净重分类改善（net reclassification improvement，NRI）提升15.28%（P=0.006）。79例浸润性尿路上皮癌中，FISH的准确率高于脱落细胞学（86.28% vs 78.32%，P=0.011）;FISH、联合检测的灵敏度均高于脱落细胞学（86.08% vs 67.09%，P=0.004;91.14% vs 67.09%，P<0.001），AUC值也高于脱落细胞学（0.808 vs 0.713，P=0.004;0.784 vs 0.713，P=0.007）;FISH与脱落细胞学相比，NRI值提升21.03%（P=0.003）。57例非浸润性尿路上皮癌中，3种检测方法的AUC值均较低（AUC<0.700）。112例高级别尿路上皮癌中，FISH的准确率、联合检测的灵敏度均高于脱落细胞学（84.94% vs 76.45%，P=0.005;89.29% vs 66.07%，P<0.001），FISH及联合检测的AUC值也均高于脱落细胞学（0.847 vs 0.752，P=0.002;0.827 vs 0.752，P=0.001），FISH比脱落细胞学的NRI值提升19.01%（P=0.003）。24例低级别尿路上皮癌中，3种检测方法的AUC值均较低（AUC<0.600）。结论：尿路上皮癌中，尤其是浸润性和高级别尿路上皮癌，FISH的诊断效能优于脱落细胞学;FISH单独检测的准确率、灵敏度与联合检测相当，且特异性高于联合检测。在非浸润性或低级别尿路上皮癌中，3种检测方法的诊断效能均较低。

关键词: 尿路上皮癌, 荧光原位杂交, 脱落细胞学, 诊断效能, 受试者工作曲线

Abstract:

Background and purpose: Urothelial carcinoma (UC) is a prevalent malignant tumor of the urinary system, and early diagnosis is crucial for improving patient prognosis. This study evaluated the diagnostic efficacy of fluorescence in situ hybridization (FISH), urine cytology and their combination for UC, as well as for its different subtypes. Methods: This study included patients who underwent transurethral resection of bladder tumor (TURBT) from January 2022 to December 2023 and approved by Ethics Commetce of Fudan Univesity Shanghai Cancer Center, No.: 050432-4-2307E) that met the inclusion and exclusion criteria. We collected TURBT pathological results and pre-procedure FISH and cytology results. Diagnostic accuracy, sensitivity and specificity of FISH, cytology and their combination were analyzed and compared for urothelial carcinoma. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and Standards for Reporting of Diagnostic Accuracy (STARD) were followed for this study. Results: A total of 283 patients were enrolled in this study, 136 were diagnosed with UC, and 147 were not. Of the 136 UC cases, 79 (58.09%) were invasive and 57 (41.91%) were non-invasive. In terms of malignancy grade, 112 (82.35%) were high-grade UC and 24 (17.65%) were low-grade UC. Using histopathology as the gold standard, the accuracy of FISH, cytology and their combination in diagnosing UC was 79.51%, 72.08% and 77.39%, respectively; sensitivity was 72.06%, 58.82% and 78.68%, respectively; specificity was 86.39%, 84.35% and 76.19%, respectively. The area under the curve (AUC) for FISH and the combination was similar but higher than that for cytology (0.792 vs 0.716, P=0.006; 0.774 vs 0.716, P=0.004); the Net Reclassification Improvement (NRI) for FISH compared to cytology was 15.28% (P=0.006). In the 79 cases of invasive UC, FISH had higher accuracy than cytology (86.28% vs 78.32%, P=0.011). The sensitivity of FISH and the combination was higher than that of cytology (86.08% vs 67.09%, P=0.004; 91.14% vs 67.09%, P<0.001), and the AUC values were also higher (0.808 vs 0.713, P=0.004; 0.784 vs 0.713, P=0.007). The NRI for FISH compared to cytology was 21.03% (P=0.003). In the 57 cases of non-invasive UC, the AUC values for all three methods were low (AUC<0.700). Among the 112 cases of high-grade UC, FISH had higher accuracy (84.94% vs 76.45%,P=0.005), and the combination had higher sensitivity (89.29% vs 66.07%, P<0.001) compared to cytology. The AUC values for FISH and the combination were also superior to that for cytology (0.847 vs 0.752, P=0.002; 0.827 vs 0.752, P=0.001). The NRI for FISH compared to cytology was 19.01% (P=0.003). In the 24 cases of low-grade UC, the AUC values for all three methods were low (AUC<0.600). Conclusion: For UC, particularly invasive and high-grade subtypes, FISH shows superior diagnostic efficacy compared to cytology. FISH alone offers accuracy and sensitivity comparable to the combination test, with higher specificity. In cases of non-invasive or low-grade UC, however, all three diagnostic methods demonstrate relatively low efficacy.

Key words: Urothelial carcinoma, Fluorescence in situ hybridization (FISH), Urine cytology, Diagnostic efficacy, Receiver operating characteristic curve

王志婷, 任敏, 薛田, 王皓晨, 常恒, 柏乾明, 周晓燕, 朱晓丽. 荧光原位杂交与尿脱落细胞学在尿路上皮癌诊断中的效能比较：一项单中心回顾性队列研究[J]. 中国癌症杂志, 2024, 34(12): 1080-1089.

WANG Zhiting, REN Min, XUE Tian, WANG Haochen, CHANG Heng, BAI Qianming, ZHOU Xiaoyan, ZHU Xiaoli. Comparison of fluorescence in situ hybridization (FISH) and urine cytology in diagnosing urothelial carcinoma: a single-center retrospective cohort study[J]. China Oncology, 2024, 34(12): 1080-1089.

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Item	TP	FP	TN	FN	Accuracy/%	χ² value	Sensitivity/%	χ² value	Specificity/%	χ² value	PPV/%	NPV/%
FISH	98	20	127	38	79.51^a	7.00^#1.04^*	72.06^a	8.03^#7.11^*	86.39	0.15^#13.07^*	83.05	76.97
Cytology	80	23	124	56	72.08	7.00^#5.03^λ	58.82	8.03^#25.04^λ	84.35	0.15^#10.08^λ	77.67	68.89
Combined	107	35	112	29	77.39	1.04^*5.03^λ	78.68^b,c	7.11^*25.04^λ	76.19^b,c	13.07^*10.08^λ	75.35	79.43

Comparison	AUC	P value	NRI	P value
FISH vs cytology	0.792 vs 0.716	0.006	15.28%	0.006
Combined vs FISH	0.774 vs 0.792	0.276	-3.58%	0.633
Combined vs cytology	0.774 vs 0.716	0.004	11.70%	0.096

Item	TP	FP	TN	FN	Accuracy/%	χ²	Sensitivity/%	χ²	Specificity/%	χ²	PPV/%	NPV/%
Invasive UC
FISH	68	20	127	11	86.28^a	6.48^#5.26^*	86.08^a	8.52^#2.25^*	86.39	0.15^#13.07^*	77.27	92.03
Cytology	53	23	124	26	78.32	6.48^#1.16^λ	67.09	8.52^#17.05^λ	84.35	0.15^#10.08^λ	69.74	82.67
Combined	72	35	112	7	81.42	5.26^*1.16^λ	91.14^b	2.25^*17.05^λ	76.19^b,c	13.07^*10.08^λ	67.29	94.12
Non-invasive UC
FISH	30	20	127	27	76.96	0.63^#4.05^*	52.63	0.31^#3.20^*	86.39	0.15^#13.07^*	60.00	82.47
Cytology	27	23	124	30	74.02	0.63^#0.45^λ	47.37	0.31^#6.13^λ	84.35	0.15^#10.08^λ	54.00	80.52
Combined	35	35	112	22	72.06	4.05^*0.45^λ	61.40^b	3.20^*6.13^λ	76.19^b,c	13.07^*10.08^λ	50.00	83.58
High-grade UC
FISH	93	20	127	19	84.94^a	8.07^#2.23^*	83.04	0.15^#5.14^*	86.39	0.15^#13.07^*	82.30	86.99
Cytology	74	23	124	38	76.45	8.07^#4.45^λ	66.07	0.15^#24.04^λ	84.35	0.15^#10.08^λ	76.29	76.54
Combined	100	35	112	12	81.85	2.23^*4.45^λ	89.29^b	5.14^*24.04^λ	76.19^b,c	13.07^*10.08^λ	74.07	90.32
Low-grade UC
FISH	5	20	127	19	77.19	0.03^#8.47^*	20.83	1.33^#0.50^*	86.39	0.15^#13.07^*	20.00	86.99
Cytology	6	23	124	18	76.02	0.03^#7.69^λ	25.00	1.33^#0.00^λ	84.35	0.15^#10.08^λ	20.69	87.32
Combined	7	35	112	17	69.59^b,c	8.47^*7.69^λ	29.17	0.50^*0.00^λ	76.19^b,c	13.07^*10.08^λ	16.67	86.82

	AUC	P value	NRI	P value
Invasive UC
FISH vs cytology	0.808 vs 0.713	0.004	21.03%	0.003
Combined vs FISH	0.784 vs 0.808	0.144	-5.14%	0.639
Combined vs cytology	0.784 vs 0.713	0.007	15.89%	0.107
Non-invasive UC
FISH vs cytology	0.695 vs 0.659	0.315	7.30%	0.323
Combined vs FISH	0.688 vs 0.695	0.752	-1.43%	0.888
Combined vs cytology	0.688 vs 0.659	0.256	5.87%	0.548
High-grade UC
FISH vs cytology	0.847 vs 0.752	0.002	19.01%	0.003
Combined vs FISH	0.827 vs 0.847	0.245	-3.95%	0.668
Combined vs cytology	0.827 vs 0.752	0.001	15.06%	0.075
Low-grade UC
FISH vs cytology	0.536 vs 0.547	0.794	-2.13%	0.794
Combined vs FISH	0.527 vs 0.536	0.766	-1.86%	0.851
Combined vs cytology	0.527 vs 0.547	0.399	-3.99%	0.712