Genetic and immunophenotype analyses of TP53 in bladder cancer: TP53 alterations are associated with tumor progression.

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 chi2 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.

ERG expression and prostatic adenocarcinoma.

ERG gene rearrangement has been identified as a highly specific alteration that is present in 40-50 % of prostate carcinomas. The standardization of an immunohistochemical assay with a novel anti-ERG antibody recently described would have significant diagnostic value. The aims of this study were to identify the incidence of this rearrangement in a Spanish population and to test the specificity of immunohistochemical ERG evaluation for prostate carcinomas. Three prostate tissue microarrays were constructed using radical prostatectomy specimens and related to grade, local invasion, and regional invasion. In addition to samples from malignant cases (160), specimens of prostatic hyperplasia (26) and high-grade prostatic intraepithelial neoplasia (10) were included. Tissue microarrays of 270 samples from most common malignant tumors (breast, colon, lung, and bladder) were also tested. All were analyzed by immunohistochemistry. Seventy-five out of 154 evaluable cases (49 %) of prostate carcinoma showed ERG expression; 52/75 showed strong staining. No ERG expression was observed in any of the high-grade prostatic intraepithelial neoplasia. ERG expression was independent of Gleason score (p = 0.160), extent of invasion (p = 0.517), and regional lymph node involvement (p = 0.816). No ERG expression was found in any other type of tumor, with the exception of one bladder cancer sample that showed focal and weak expression. The frequency of ERG detected in our study correlated with the results published for other Caucasian populations. Strong ERG protein expression was exclusively detected in prostate carcinomas, corroborating the specificity of ERG rearrangements for these tumors. Thus, detecting ERG using immunohistochemistry may be useful in routine practice in pathology departments.