Telomerase activity as a potential marker in preneoplastic bladder lesions

Abstract

Objective 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. Patients and methods 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. Results 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. Conclusion 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.

Clinical utility of telomerase in cancer

“…Telomerase activity is a useful indicator to determine malignant grade in the group of tumors in which benign and malignant tumors are sometimes indistinguishable by morphological examination such as brain tumors (Falchetti et al, 1999;Langford et al, 1997), papillary adenocarcinoma in thyroid (Matthews et al, 2001), pancreatic endocrine tumors (Pearson et al, 2000), urothelial cell carcinoma (Lancelin et al, 2000), and cervical intraepithelial neoplasia (Wisman et al, 2001). In these tumors, the levels of telomerase activity subsequently correlated to the prognosis of the patients.…”

Telomerase: Its clinical relevance in the diagnosis of bladder cancer

“…It was shown that, regardless of tumour stage or degree of di erentiation, telomerase activity could be identi®ed in nearly all tissue samples derived from bladder carcinomas (Table 1) but not in normal urothelium. Thus, the fundamental prerequisites for a diagnostic method with high sensitivity and speci®city are ful®lled (Gelmini et al, 2000;Ito et al, 1998a;Kamata et al, 1996;Kinoshita et al, 1997;Kyo et al, 1997;Lancelin et al, 2000;Lee et al, 1998;Lin et al, 1996;Linn et al, 1997;May®eld et al, 1998;MuÈ ller et al, 1996;Rahat et al, 1999;Yokota et al, 1998;Yokota et al, 1998;Yokota et al, , 1996), low levels of telomerase activity were identi®ed in dysplastic urothelium by Lin et al (1996) in one of two cases and by Yoshida et al (1997) in two of two cases. In a very small number of cases, telomerase activity was detected in histologically normal urothelial tissue immediately adjacent to con®rmed tumours.…”

“…In a very small number of cases, telomerase activity was detected in histologically normal urothelial tissue immediately adjacent to con®rmed tumours. This was probably due to the presence of individual tumour cells or tumour precursors that had escaped detection with conventional light microscopy (Kyo et al, 1997;Lancelin et al, 2000).…”

Telomerase activity in bladder cancer tissue

“…an association between telomerase activity and pathological grade or stage in bladder cancer patients has also been demonstrated (5,6,12). Lin et al reported that the expression of telomerase activity was clearly associated with pathological grade and stage (12).…”

“…Telomerase activity is assumed to be involved in the maintenance of telomere length, and its reactivation is required for cell immortalization. telomerase activity has been reported in many human cancers (5). One study reported a correlation between telomerase activity in bladder cancer tissue and tumor grade or stage (6).…”