Prognostic significance of transcription factor E2F-1 in bladder cancer: Genotypic and phenotypic characterization Journal Article
| Authors: | Rabbani, F.; Richon, V. M.; Orlow, I.; Lu, M. L.; Drobnjak, M.; Dudas, M.; Charytonowicz, E.; Dalbagni, G.; Cordon-Cardo, C. |
| Article Title: | Prognostic significance of transcription factor E2F-1 in bladder cancer: Genotypic and phenotypic characterization |
| Abstract: | Background: We sought to identify and characterize potential alterations in E2F-1, a transcription factor that binds to the retinoblastoma protein (pRB), in bladder neoplasms and to elucidate a possible role for E2F-1 as an oncogene or a tumor suppressor gene. Methods: Tumor samples from 133 evaluable patients with bladder cancer were analyzed for E2F-1 gene mutations by use of polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing. In addition, tumors were studied for E2F-1 and pRB protein expression by use of immunohistochemistry. Results from the above analyses were correlated with clinicopathologic parameters and outcome. All P values are two-sided. Results: A polymorphism, consisting of a nucleotide change at amino acid codon 393 in exon 7 (GGC→AGC [Gly→Ser]), was identified in seven of 133 case patients, being present in both tumor and corresponding normal tissues. No band-shifts were identified in the nuclear- localization or DNA-binding domains on PCR-SSCP analysis. On immunohistochemical analysis, E2F-1 nuclear reactivity was observed in less than 5% of the cells from 53 tumors and in 5%75% of the cells from the remaining 80 tumors. The pattern of E2F-1 protein expression was not altered in relation to the identified polymorphism. pRB nuclear reactivity greater than 20% (of tumor cells stained) was present in 66% of the samples. E2F-1 nuclear reactivity correlated inversely with the percentage of cells showing pRB reactivity (Kendall τ(b)=-0.18; P = .019). On multivariate analysis, patients with lower E2F-1 reactivity had statistically significantly increased risks of progression to metastases (P = .001) and death (P = .02). Conclusions: E2F-1 alterations occur at the phenotypic level, rather than at the genotypic level, in bladder cancer. The adverse outcome for patients whose tumors exhibit low E2F-1 nuclear expression suggests a possible tumor suppressor role for E2F-1 in bladder cancer. |
| Keywords: | immunohistochemistry; adult; aged; gene mutation; major clinical study; gene deletion; mutation; dna-binding proteins; lymphatic metastasis; neoplasm staging; polymerase chain reaction; phenotype; cell cycle proteins; serine; protein binding; genotype; bladder cancer; urinary bladder neoplasms; transcription factors; tumor suppressor gene; transcription factor e2f; carrier proteins; carcinoma; multivariate analysis; neoplasm invasiveness; retinoblastoma protein; glycine; genetic polymorphism; transcription factor dp1; e2f1 transcription factor; single strand conformation polymorphism; polymorphism, single-stranded conformational; e2f transcription factors; humans; prognosis; human; male; female; priority journal; article |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 91 |
| Issue: | 10 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 1999-05-19 |
| Start Page: | 874 |
| End Page: | 881 |
| Language: | English |
| PUBMED: | 10340908 |
| PROVIDER: | scopus |
| DOI: | 10.1093/jnci/91.10.874 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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