Hartmann A, Moser K, Kriegmair M, Hofstetter A, Hofstaedter F, Knuechel R
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Am J Pathol. 1999 Mar;154(3):721-7. doi: 10.1016/S0002-9440(10)65318-7.
In order to understand the origin of bladder cancer, very early urothelial lesions must be investigated in addition to more advanced tumors. Tissue from 31 biopsies of 12 patients with urothelial hyperplasias and simultaneous or consecutive superficial papillary tumors were used to microdissect urothelium from 15- microm sections of biopsies. The biopsies were obtained with the recently developed highly sensitive diagnostic method of 5-aminolevulinic acid-induced fluorescence endoscopy (AFE). Besides flat and papillary urothelial neoplasms, the method of photodynamic diagnostics also detects simple urothelial hyperplasias as fluorescent positive lesions. In addition, 12 fluorescence-positive biopsies showing histologically normal urothelium were investigated. Fluorescence in situ hybridization was done using a dual color staining technique of biotinylated centromeric probes of chromosomes 9 and 17 and digoxigenin-labeled gene-specific P1 probes for chromosomes 9q22 (FACC), 9p21(p16/CDKI2), and 17p13(p53). Ten of 14 hyperplasias (70%) showed deletions of chromosome 9. In 7 out of 8 patients with genetic alterations in the hyperplasias the genetic change was also present in the papillary tumor. Six out of 12 samples of microdissected normal urothelium also showed genetic alterations on chromosome 9. Microdissection of urothelial lesions, obtained during AFE, has led to the first unequivocal documentation of genetic changes in urothelial lesions diagnosed as normal in histopathology. Thus, this technical approach is important to provide insight into the earliest molecular alterations in bladder carcinogenesis.
为了了解膀胱癌的起源，除了更晚期的肿瘤外，还必须对非常早期的尿路上皮病变进行研究。来自12例尿路上皮增生患者的31份活检组织以及同时或相继出现的浅表乳头状肿瘤，用于从活检组织的15微米切片中显微切割尿路上皮。活检组织是通过最近开发的高灵敏度5-氨基乙酰丙酸诱导荧光内镜检查（AFE）诊断方法获取的。除了扁平状和乳头状尿路上皮肿瘤外，光动力诊断方法还能将单纯的尿路上皮增生检测为荧光阳性病变。此外，还对12份组织学上显示尿路上皮正常的荧光阳性活检组织进行了研究。荧光原位杂交采用双色染色技术，使用生物素化的9号和17号染色体着丝粒探针以及地高辛标记的9q22（FACC）、9p21（p16/CDKI2）和17p13（p53）染色体基因特异性P1探针。14例增生中有10例（70%）显示9号染色体缺失。在增生中发生基因改变的8例患者中，有7例乳头状肿瘤也存在基因改变。12份显微切割的正常尿路上皮样本中有6份也显示9号染色体存在基因改变。在AFE过程中获取的尿路上皮病变的显微切割，首次明确记录了组织病理学诊断为正常的尿路上皮病变中的基因变化。因此，这种技术方法对于深入了解膀胱癌发生过程中最早的分子改变具有重要意义。
