Analysis of progress of grades in urinary bladder cancer : telomere measurement with original software and chromosomal instability

为了评估尿路上皮肿瘤的三种组织学类型、染色体不稳定性和端粒长度之间存在的关系，我们检查了37例连续的乳头状尿路上皮肿瘤，从中我们获得了26例（70.3%）适合于核型分析，包括7例PUNLMP，10例低度乳头状尿路上皮癌（PUCs）和9例高度PUCs。我们对这些病例进行了核型分析和后期桥分析，并通过Q-FISH测量了他们的端粒长度。PUNLMP均为二倍体，并有后期桥。低级别PUC表现为二倍体（n = 2）、亚倍体（n = 4）和多倍体（n = 4），高级别PUC表现为二倍体（n = 1）和多倍体（n = 8）;两者均存在后期桥。PUNLMP和高级别PUC之间后期桥的发生率没有显著差异（p = 0.105）。PUNLMP、低级别PUC和高级别PUC的端粒长度（以平均端粒荧光单位（TFU）± SD表示）分别为7906 ± 3197、4893 ± 1567和3299 ± 1406。三组间差异有统计学意义。然而，42.9%的PUNLMP的端粒短于低级别PUC的平均值，30.0%的低级别PUC的端粒短于高级别PUC的端粒。端粒长度与后期桥的发生率呈负相关。这表明，PUNLMP进展到低和高级别PUC与端粒缩短和染色体不稳定性。我们的数据支持这样的观点，即在乳头状尿路上皮肿瘤的进展过程中，严重缩短的端粒会导致染色体不稳定。

In order to evaluate the relationships existing among three histologic types of urothelial tumors, chromosomal instability, and telomere length, we examined 37 consecutive cases of papillary urothelial neoplasm, from which we obtained 26 (70.3%) that were suitable for karyotype analysis, comprising 7 PUNLMP, 10 low-grade papillary urothelial carcinomas (PUCs), and 9 high-grade PUCs. We subjected these cases to karyotype and anaphase bridge analyses, and measured their telomere lengths by Q-FISH. PUNLMP always showed diploidy and had anaphase bridges. Low-grade PUC showed diploidy (n = 2), hypoploidy (n = 4) and polyploidy (n = 4), and high-grade PUC revealed diploidy (n = 1) and polyploidy (n = 8); both had anaphase bridges. The incidence of anaphase bridges did not differ significantly between PUNLMP and high-grade PUC (p = 0.105). The telomere lengths of PUNLMP, low-grade PUC, and high-grade PUC, expressed as mean telomere fluorescence units (TFU) ± SD, were 7906 ± 3197, 4893 ± 1567, and 3299 ± 1406, respectively. The differences among the three groups were significant. However, 42.9% of PUNLMPs had shorter telomeres than the mean value for low-grade PUC, and 30.0% of the low-grade PUCs had shorter telomeres than those for high-grade PUC. There was an inverse correlation between telomere length and the incidence of anaphase bridges. It is suggested that PUNLMP progresses to low- and high-grade PUC in association with telomere shortening and chromosomal instability. Our data support the idea that critically shortened telomeres cause chromosomal instability during progression of papillary urothelial neoplasms..