Amira Najla, Rivet Jacqueline, Soliman Hany, Cancel-Tassin Geraldine, Le Duc Alain, Janin Anne, Cussenot Olivier
Centre de Recherche sur les Pathologies Prostatiques, Equipe d'Accuil 3104, Départments d'Urologie, C.H.U. Saint-Louis, Evry, France.
J Urol. 2003 Oct;170(4 Pt 1):1151-4. doi: 10.1097/01.ju.0000086551.22844.cd.
Transitional cell carcinoma (TCC) of the upper urinary tract (TCC-UUT) may develop with high frequency in patients with hereditary nonpolyposis colorectal cancer syndrome. Tumors in patients with this syndrome show genomic lesions in DNA mismatch repair genes that are detectable as microsatellite instability (MSI). Because little is known about genetic lesions in TCC-UUT compared with bladder TCC, we determined the genetic profiles (MSI and allelic loss) in a series of 26 upper urinary tract tumors using 5 informative microsatellite markers.
A total of 26 paraffin embedded samples from 24 patients with clinically diagnosed TCC-UUT (renal pelvis and/or ureter) were tested for loss of heterozygosity (LOH) and MSI with the dinucleotide markers D9S171 (9p21) and D5S346 (5q22), and the mononucleotide repeats BAT25 (4q12), BAT26 (2p16) and BAT40 (1p13.1).
MSI was detected at 1 or more microsatellite loci in 12 of the 26 tumors (46%). The markers BAT40, BAT25, BAT26, D9S171 and D5S346 showed instability in 7, 4, 4, 2 and 3 tumor samples, respectively. LOH at D9S171 was detected in 58% of the cases and 10 of the 14 tumors showing LOH were superficial. LOH at D5S346 occurred in 27% of the cases and it was a feature of invasive high grade TCC-UUT.
Frequent LOH at D9S171 in TCC-UUT confirms that LOH at 9p21 is not only observed in bladder TCC, but rather in whole urinary tract TCC. Furthermore, our study indicates a high level of MSI in TCC-UUT, although it is a rare event in bladder cancer. The establishment of distinct genetic profiles between upper and lower urinary tract tumors could provide an additional tool to improve diagnosis, disease monitoring and prediction of prognosis.
遗传性非息肉病性结直肠癌综合征患者上尿路移行细胞癌（TCC-UUT）的发病率可能较高。该综合征患者的肿瘤在DNA错配修复基因中表现出基因组损伤，可检测为微卫星不稳定性（MSI）。由于与膀胱TCC相比，对TCC-UUT中的基因损伤了解较少，我们使用5个信息性微卫星标记物确定了一系列26例上尿路肿瘤的基因谱（MSI和等位基因缺失）。
对24例临床诊断为TCC-UUT（肾盂和/或输尿管）患者的26个石蜡包埋样本进行杂合性缺失（LOH）和MSI检测，使用二核苷酸标记物D9S171（9p21）和D5S346（5q22），以及单核苷酸重复序列BAT25（4q12）、BAT26（2p16）和BAT40（1p13.1）。
26个肿瘤中有12个（46%）在1个或更多微卫星位点检测到MSI。标记物BAT40、BAT25、BAT26、D9S171和D5S346分别在7、4、4、2和3个肿瘤样本中显示出不稳定性。58%的病例检测到D9S171的LOH，14个显示LOH的肿瘤中有10个为浅表性肿瘤。D5S346的LOH发生在27%的病例中，是侵袭性高级别TCC-UUT的一个特征。
TCC-UUT中D9S171频繁出现LOH证实，9p21的LOH不仅在膀胱TCC中观察到，而且在整个尿路TCC中也存在。此外，我们的研究表明TCC-UUT中MSI水平较高，尽管在膀胱癌中这是一个罕见事件。上尿路和下尿路肿瘤之间不同基因谱的建立可为改善诊断、疾病监测和预后预测提供额外的工具。
