Lancelin F, Anidjar M, Villette J M, Soliman A, Teillac P, Le Duc A, Fiet J, Cussenot O
Laboratoire de Biologie Hormonale, Département d'Urologie, Hôpital St Louis, Paris, France.
BJU Int. 2000 Mar;85(4):526-31. doi: 10.1046/j.1464-410x.2000.00466.x.
To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis.
Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol-polymerase chain reaction (TRAP-PCR) and a telomerase PCR-enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder.
Eleven of the 14 tumour samples analysed were telomerase-positive and two of the three telomerase-negative tumour samples had a detectable 'telomerase inhibitor'. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase-positive. Interestingly, these lesions were always next to high-grade muscle-invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase-positive.
These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.
评估端粒酶活性(参与细胞永生化,在大多数恶性肿瘤中可检测到,但在正常体细胞组织中未检测到)作为癌症诊断的标志物。
采用两种不同技术检测组织端粒酶活性,即端粒重复序列扩增法-聚合酶链反应(TRAP-PCR)和端粒酶PCR-酶联免疫吸附测定法。对18例患者的恶性和炎性膀胱病变及其相邻正常组织进行端粒酶活性评估,其中14例患有尿路上皮癌,4例患有膀胱非特异性炎性病变。
分析的14个肿瘤样本中有11个端粒酶呈阳性,3个端粒酶阴性的肿瘤样本中有2个检测到“端粒酶抑制剂”。在膀胱肿瘤旁看似正常的组织中,14个样本中有4个端粒酶呈阳性。有趣的是,这些病变总是紧邻高级别肌层浸润性膀胱肿瘤(pT2G3)。4例非特异性炎性病变中有2例(1例腺性膀胱炎和1例重度发育异常),已知为癌前病变,端粒酶也呈阳性。
这些结果强烈表明,端粒酶的重新激活可能是膀胱癌发生的早期事件,早于与恶性转化相关的形态学变化。因此,端粒酶活性既可用作癌前病变(如腺性膀胱炎和重度发育异常)恶性潜能的指标,也可用作膀胱肿瘤复发或进展的预后标志物。