| Abstract: |
Altered p53 status is a frequent event in bladder cancer and reported to have prognostic significance. We studied the TP53 gene and its product in 76 patients affected with urinary bladder carcinomas by immunohistochemistry (mAb DO-7), polymerase chain reaction single-strand conformational polymorphism (exons 4-8) followed by direct sequencing of shifted bands, and loss of heterozygosity in 17p (p53CA). H-RAS mutations were also studied. The receiver operating characteristic curve and the logistic-regression analysis were used to evaluate the validity of immunohistochemistry in predicting TP53 mutations. A p53-positive nuclear phenotype was defined by a cutoff of 20% tumor cells being immunoreactive and was found in 23 cases, while TP53 mutations were detected in 22 cases, four of them with a negative p53 phenotype. TP53 deletions were identified in 23 cases. No H-RAS gene mutations were observed. There was a significant association between phenotype and genotype results. Moreover, a significant association was observed between p53 status and tumor stage and grade, being alterations more common in high-stage and high-grade tumors (both χ2 test; P < .01). Deletion of 17p significantly correlated with tumor stage (P < .01) and grade (P = .01), allelic losses being more common in advanced disease. Data from these studies suggest that genetic assays are necessary for the optimal determination of TP53 alterations, mainly in tumors with a p53 negative phenotype, and especially in early stage tumors for which p53 status may assist in determining its progression to invasive disease. Since p53 alterations are significantly associated to clinicopathological features of poor prognosis, the inclusion of both p53 phenotype and TP53 mutation status into a predictive panel of tumor markers for bladder cancer is recommended. |
| Keywords: |
immunohistochemistry; adult; human tissue; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; gene deletion; cancer growth; validation process; prospective studies; genetic analysis; polymerase chain reaction; tumor markers, biological; genotype; immunoreactivity; bladder cancer; protein p53; tumor marker; urinary bladder neoplasms; disease progression; dna, neoplasm; tumor suppressor protein p53; immunophenotyping; heterozygosity loss; dna mutational analysis; loss of heterozygosity; carcinoma, transitional cell; logistic regression analysis; receiver operating characteristic; chromosomes, human, pair 17; h-ras; tp53 mutations; single strand conformation polymorphism; polymorphism, single-stranded conformational; humans; human; male; female; priority journal; article; 17p allelic losses
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