title: Molecular genetic alterations of chromosome 17 and p53 nuclear overexpression in human bladder cancer.
abstract: We set out to define the alterations of chromosome 17 in human bladder tumors and to correlate p53 nuclear over-expression with 17p deletions in those neoplasms. We studied 60 bladder tumors by restriction fragment-length polymorphism analysis directed at five different loci on chromosome 17. The same tumors were studied with a panel of mouse monoclonal antibodies (PAb1801, PAb240, and PAb1620) to mutant and wild-type p53 proteins using immunohistochemistry. Deletion of 17p correlated with grade (p = 0.039), stage (p = 0.004), and the presence of vascular invasion (p = 0.056). None of the pathologic parameters correlated with 17q deletions. p53 nuclear overexpression correlated with grade (p = 0.027), stage (p = 0.008), vascular invasion (p = 0.021), and the presence of nodal metastases (p = 0.007). In superficial (Ta) lesions, 17p was not deleted, whereas 55% of T1 and T2-T4 tumors showed a loss of heterozygosity. Mutations of p53 as detected by immunohistochemistry were seen in superficial as well as invasive tumors, whereas loss of heterozygosity was seen only in invasive tumors. A strong correlation was found between the presence of mutation and the loss of heterozygosity of the remaining allele (p = 0.0003). 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.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: G
authors.initials: G
authors.lastname: Dalbagni
authors.forename: J C
authors.initials: JC
authors.lastname: Presti
authors.forename: V E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhang
authors.forename: A S
authors.initials: AS
authors.lastname: Sarkis
authors.forename: W R
authors.initials: WR
authors.lastname: Fair
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
mesh_terms: D000483:Alleles; D002886:Chromosomes, Human, Pair 17 / Q000737:chemistry*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D015994:Incidence; D009154:Mutation / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53