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

为了探讨尿路上皮肿瘤的三种组织学类型与染色体不稳定性和端粒长度的关系，我们对37例尿路上皮乳头状瘤进行了分析，从中获得26例(70.3%)适合进行核型分析，其中PUNLMP 7例，低度乳头状尿路上皮癌(PUC)10例，高度恶性PUC 9例。我们对这些病例进行了核型和后期桥分析，并用Q-FISH测量了它们的端粒长度。PUNLMP始终呈二倍体，并有后期桥。低度恶性PUC有二倍体(n=2)、亚倍体(n=4)和多倍体(n=4)，高度恶性PUC有二倍体(n=1)和多倍体(n=8)，均有后期桥。晚期桥在PUNLMP和高级别PUC中的发生率无显著差异(p=0.105)。以平均端粒荧光单位(TFU)±SD表示的PUNLMP、低度恶性PUC和高度恶性PUC的端粒长度分别为7906±3197、4893±1567和3299±1406。三组间差异有统计学意义。但42.9%的PUNLMP端粒长度低于低度恶性PUC的平均值，30.0%的低度恶性PUC端粒长度短于高度恶性PUC。端粒长度与后期桥的发生率呈负相关。提示PUNLMP进展为低级别和高级别的PUC，与端粒缩短和染色体不稳定有关。我们的数据支持这样一种观点，即在乳头状尿路上皮肿瘤的进展过程中，端粒严重缩短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..