PMID- 20362225 OWN - NLM STAT- MEDLINE DCOM- 20100426 LR - 20220331 IS - 1873-4456 (Electronic) IS - 0165-4608 (Linking) VI - 198 IP - 2 DP - 2010 Apr 15 TI - Analysis of fluorescence in situ hybridization, mtDNA quantification, and mtDNA sequence for the detection of early bladder cancer. PG - 107-17 LID - 10.1016/j.cancergencyto.2009.12.017 [doi] AB - We designed this study to test the sensitivities of cytology, the nuclear matrix protein 22 (NMP22) assay, and fluorescence in situ hybridization (FISH) in the early detection of urothelial carcinoma, and to identify mtDNA alterations in urinary epithelial cells. We collected 41 urine samples and 26 corresponding peripheral blood samples from patients with clinically suspected urothelial carcinoma. The FISH and NMP22 assays detected 92.1% of the cancers, and cytology detected 60.5%. In the low-grade group, NMP22 and FISH analyses were more sensitive than cytology, but in the high-grade group, all three methods showed approximately 90% sensitivity. Overall, the FISH and NMP22, or FISH and cytology assays combined detected 97.4% of cancers, while cytology with NMP22 detected 92.1%. In the low-grade group, the sensitivity of the three methods combined was above 80%, but in high-grade group, the combined sensitivity was approximately 100%. In the mtDNA control region, we detected characteristic heteroplasmic mtDNA substitution mutations in 1 patient and a mtDNA length heteroplasmic mutation in 303 polyC or 16184 poly C in 20 patients. Overall, urothelial carcinoma-specific mtDNA mutations were observed in 20 of the 26 patients (76.9%). The average mtDNA copy numbers in urine samples and corresponding peripheral blood samples (83.45 +/- 60.36 and 39.0 +/- 24.38, respectively) (mean +/- standard deviation [SD]) differed significantly (P < 0.001). The mtDNA copy numbers in the urine samples from patients with high-grade and low-grade tumors (81.83 +/- 67.78 and 86.49 +/- 46.69, respectively) did not differ significantly (P = 0.589). In conclusion, the FISH assay showed the highest sensitivity for detecting low-grade urothelial carcinoma, and mtDNA copy numbers in urine samples were higher than those in the corresponding peripheral blood samples. The frequency of mtDNA mutations in the D-loop region in patients with cancer was approximately 80% in our study. This report further supports the significance of genetic alteration in urothelial carcinoma and the clinical utility of the FISH, mtDNA quantitation polymerase chain reaction, mtDNA sequencing, and capillary electrophoresis for this purpose. CI - Copyright 2010 Elsevier Inc. All rights reserved. FAU - Yoo, Jong-Ha AU - Yoo JH AD - Department of Laboratory Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang-si, Kyonggi-do, 410-719, Korea. FAU - Suh, Borum AU - Suh B FAU - Park, Tae Sung AU - Park TS FAU - Shin, Myung-Geun AU - Shin MG FAU - Choi, Yeung Deuk AU - Choi YD FAU - Lee, Chang Hoon AU - Lee CH FAU - Choi, Jong Rak AU - Choi JR LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Genet Cytogenet JT - Cancer genetics and cytogenetics JID - 7909240 RN - 0 (DNA, Mitochondrial) RN - 0 (Nuclear Proteins) RN - 0 (nuclear matrix protein 22) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma/blood/*diagnosis/genetics/pathology MH - DNA Mutational Analysis/methods MH - DNA, Mitochondrial/*analysis/genetics MH - Early Detection of Cancer/*methods MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence/*methods MH - Male MH - Middle Aged MH - Nuclear Proteins/analysis/genetics MH - Sensitivity and Specificity MH - Sequence Analysis, DNA/methods MH - Urinary Bladder Neoplasms/blood/*diagnosis/genetics/pathology MH - Young Adult EDAT- 2010/04/07 06:00 MHDA- 2010/04/27 06:00 CRDT- 2010/04/06 06:00 PHST- 2009/09/08 00:00 [received] PHST- 2009/11/23 00:00 [revised] PHST- 2009/12/30 00:00 [accepted] PHST- 2010/04/06 06:00 [entrez] PHST- 2010/04/07 06:00 [pubmed] PHST- 2010/04/27 06:00 [medline] AID - S0165-4608(10)00006-3 [pii] AID - 10.1016/j.cancergencyto.2009.12.017 [doi] PST - ppublish SO - Cancer Genet Cytogenet. 2010 Apr 15;198(2):107-17. doi: 10.1016/j.cancergencyto.2009.12.017.