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通过流式细胞术和荧光原位杂交检测膀胱癌中的DNA畸变。

DNA aberrations in urinary bladder cancer detected by flow cytometry and FISH.

作者信息

Sauter G, Gasser T C, Moch H, Richter J, Jiang F, Albrecht R, Novotny H, Wagner U, Bubendorf L, Mihatsch M J

机构信息

Institute for Pathology, University of Basel, Switzerland.

出版信息

Urol Res. 1997;25 Suppl 1:S37-43. doi: 10.1007/BF00942046.

Abstract

Detection of molecular alterations is of potential significance for diagnosis and prognosis in bladder cancer. Fluorescence in situ hybridization (FISH) allows visualization and quantitation of genes and chromosomes on a cell by cell level and can easily be applied to urinary cells. To evaluate the sensitivity of FISH for detection of DNA aberrations in bladder cancer, formalin-fixed tissues of 293 tumors were examined by FISH and flow cytometry (FCM). Centromere probes for the chromosomes X, Y, 1, 7, 9, and 17 were used for FISH analysis. FISH was more sensitive for detection of quantitative DNA aberrations than FCM. An aberration of at least one chromosome was found in 107 of 108 tumors (99%), which were tetraploid, aneuploid, or multiploid, and in 29 of 49 tumors (59%), which were diploid, by FCM. The frequency of FISH aberrations showed greater differences between pTa (47%) and pT1 tumors (85%; P < 0.0001) than between stages pT1 and pT2-4 (98%). The marked genetic difference between pTa and pT1 tumors argues against the concept of grouping pTa and pT1 tumors together as "superficial bladder cancer." The frequency of tumors with chromosomal aberrations detected by FISH increased with the number of chromosomes examined. Aneusomy was seen in 68% of grade 1 tumors examined for > or = 4 chromosomes, suggesting that the cytological diagnosis of bladder cancer recurrences could be substantially improved by FISH.

摘要

检测分子改变对膀胱癌的诊断和预后具有潜在意义。荧光原位杂交(FISH)可在细胞水平上对基因和染色体进行可视化和定量分析,并且能够轻松应用于尿路上皮细胞。为了评估FISH检测膀胱癌DNA畸变的敏感性,采用FISH和流式细胞术(FCM)对293例肿瘤的福尔马林固定组织进行检测。使用针对X、Y、1、7、9和17号染色体的着丝粒探针进行FISH分析。FISH检测定量DNA畸变比FCM更敏感。通过FCM检测发现,108例四倍体、非整倍体或多倍体肿瘤中有107例(99%)存在至少一条染色体的畸变,49例二倍体肿瘤中有29例(59%)存在染色体畸变。FISH检测到的畸变频率在pTa期(47%)和pT1期肿瘤(85%;P < 0.0001)之间的差异大于pT1期和pT2 - 4期(98%)之间的差异。pTa期和pT1期肿瘤之间明显的基因差异反对将pTa期和pT1期肿瘤归为“浅表性膀胱癌”的概念。FISH检测到的染色体畸变肿瘤频率随检测染色体数量的增加而升高。在检测≥4条染色体的1级肿瘤中,68%存在非整倍体,这表明FISH可显著改善膀胱癌复发的细胞学诊断。

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