Our findings support suggestions that (i) inactivation of p53 and/or pRb constitutes a causal step in the etiology of invasive TCC, (ii) papillary and invasive TCC may have different molecular causes, and (iii) carcinoma in situ can represent an early stage in the progression to invasive TCC.
Longitudinal study of Tp53 mutation in urine sediments of 26 patients with mutated primary transitional cell carcinoma (TCC) of the urinary bladder at different time periods after transurethral resection of the bladder (TURB), i.e. before and after the first TURB, prior to the control resection and before treatment of a recurrence.
The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations.
We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their relationship to the development of multifocal TCC.
These results indicate that the SV40T inactivation of p53 and retinoblastoma gene products, defects frequently found in human bladder CIS and invasive TCCs, can cause the aggressive form of TCC.
Multivariate analysis revealed only T category (P = 0.01095266), lymph node involvement (P = 0.00054877), and p53 positivity (P = 0.0316974) to be independent prognostic factors in muscle invasive SCC and TCC.
Also, more polysomic TCCs were found in muscle-invasive than in superficial cases (P< 0.01 ), and there was a difference in both p53 overexpression or PCNA-LI between disomic and polysomic TCCs (P< 0.01).
We have used microdissection of paraffin-embedded histological sections and polymerase chain reaction (PCR)-based direct DNA sequencing for 54 transitional cell carcinoma (TCC) of the bladder, to examine critically the association between TP53 nuclear accumulation determined by immunohistochemistry and the presence of TP53 mutations, and to examine their relationship to tumour stage and grade, as well as patient survival.
In this study, four of six myoinvasive TCCs also showed TP53 mutation that associated well with genome instability (P = 0.001), as previously hypothesized.
PCR-single-strand conformation polymorphism analysis demonstrated that mutations (a) occurred in both dysplasia and in normal-looking epithelium, in addition to TCC lesions; (b) were at different sites in the p53 gene in concurrent or metachronous lesions; and (c) occurred in exon 5 in approximately 70% of lesions, especially at codons 151 and 152.
In this study, the authors determined the prognostic significance of proliferating cell nuclear antigen (PCNA), p53 protein, and nm23 protein, as well as nuclear DNA content in specimens with TCC of the bladder.
Here, the p21WAF1/CIP1 gene, a p53 inducible and p53 independent gene product, was studied in TCC. p21WAF1/CIP1 expression was measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from five cell lines and 28 tumor specimens (14 superficial, 14 muscle invasive).
Thirteen of 28 patients (46%) with grade 2-3 multifocal transitional cell carcinoma (TCC) of the bladder were found to have p53 mutations using DNA sequence analysis.
However, the proliferative activity in itself rather than the effect due to a specific alteration in p53 plays an important role in the development and progression in TCC of the bladder.
Abnormal accumulation of p53 protein was found in 24/47 (51%) carcinomas. p53 positivity was found significantly more often in SCC than in TCC (p = 0.05).
Patients with p53-positive invasive TCCs showed statistically significant worse survival (P = 0.007), but in multivariate analysis, p53 positivity is not independently related to poor overall survival (P = 0.30).
Recent investigations have demonstrated alterations of the p53 tumor-suppressor gene in a considerable number of transitional-cell carcinoma (TCC) specimens.
The type and position of the mutations were not significantly different when compared with the spectra of p53 mutations previously reported for transitional cell carcinomas (TCCs).
Fifty-one of the tumours were p53 positive. p53 positive tumours were significantly more often found in TCC with low SPFs than in those with high SPFs.