Additional follow-up and further studies are required to better define the role of p53 nuclear overexpression and 17p deletions as markers of tumor progression in human bladder cancer.
After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53.
Alterations in p53 represent one of the most common genetic events in patients with invasive urothelial carcinoma and are suggested to be linked to tumor progression, prognosis, and chemosensitivity. p53 possesses various functions, including induction of cell-cycle arrest, apoptosis, DNA repair, and antioxidants; it acts as a killer and a healer.
Alterations in p53 and pRb, products of the chromosomes 17p13 TP53 and 13q14 RB tumor suppressor genes, occur in approximately 50% and approximately 33% of bladder cancers respectively, and are associated with later stage, higher grade disease. p53 and pRb alterations are also known to occur in early stage bladder carcinoma in situ where they are thought to represent a poor prognosis for tumor progression.
Although p53 mutations in anaplastic Wilms' tumors have been associated with chemoresistance, this event is believed to occur late during tumor progression.
Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53.
Although colorectal cancer cells are characterized by specific microsatellite alterations, the same four different signalling pathways, WNT/Wingless pathway, K-ras pathway, transforming growth factor (TGF)beta pathway and p53 pathway, could be implicated in tumour progression.
Although its standard functions are strongly connected to tumor suppression, p53 mutants and aggregates are involved in cancer progression. p53 aggregates are heterogeneous assemblies composed of amorphous aggregates, oligomers, and amyloid-like fibrils.
Although mutation or inactivation of the p53 tumor suppressor gene occurs at early stages in gliomas and is associated with tumor progression, many tumors including high-grade glioblastoma multiforme carry a functionally intact p53 gene.
Although the ATM and p53 pathways overlap, they are not congruent, and it is unclear how the mechanism of tumor progression differs between ATM- and p53-deficient tumors.
Altogether, N-ras p21 alterations are registered at earlier stages than p53 alterations in melanoma development and may be of aetiological importance, whereas p53 alterations may be associated with tumour progression in the late stages.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup.