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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The National Cancer Institute Bladder Tumor Marker Network conducted a study to evaluate the reproducibility of immunohistochemistry for measuring p53 expression in bladder tumors. Fifty paraffin blocks (10 from each of the five network institutions) were chosen at random from among high-grade invasive primary bladder tumors. Two sections from each block were sent to each laboratory for staining and scoring, and then all sections were randomly redistributed among the laboratories for a second scoring. Intra- and interlaboratory reproducibility was assessed with regard to both staining and scoring. For overall assessments of p53 positivity, the results demonstrated that intralaboratory reproducibility was quite good. Concordance across the five participating laboratories was high for specimens exhibiting no or minimal nuclear immunostaining of tumor cells or high percentages of tumor cells with nuclear immunoreactivities. However, there was a reduced level of concordance on specimens with percentages of stained tumor cells in an intermediate range. The discordancies were due mainly to staining differences in one of the five laboratories and scoring differences in another laboratory. These results indicate that some caution must be used in comparing results across studies from different groups. Standardization of staining protocols and selection of a uniform threshold for binary interpretation of results may improve assay reproducibility between laboratories.
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PMID:Reproducibility of p53 immunohistochemistry in bladder tumors. National Cancer Institute, Bladder Tumor Marker Network. 1081 8

We have screened for mutations in exons 5-8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1-G2a) and 106 (56%) were highly malignant (G2b-G4 or > or = T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant.
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PMID:p53 mutations in urinary bladder cancer. 1138 1

Improved characterization of tumors for purposes of guiding treatment decisions for cancer patients will require that accurate and reproducible assays be developed for a variety of tumor markers. No gold standards exist for most tumor marker assays. Therefore, estimates of assay sensitivity and specificity cannot be obtained unless a latent class model-based approach is used. Our goal in this article is to estimate sensitivity and specificity for p53 immunohistochemical assays of bladder tumors using data from a reproducibility study conducted by the National Cancer Institute Bladder Tumor Marker Network. We review latent class modeling approaches proposed by previous authors, and we find that many of these approaches impose assumptions about specimen heterogeneity that are not consistent with the biology of bladder tumors. We present flexible mixture model alternatives that are biologically plausible for our example, and we use them to estimate sensitivity and specificity for our p53 assay example. These mixture models are shown to offer an improvement over other methods in a variety of settings, but we caution that, in general, care must be taken in applying latent class models.
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PMID:Latent class modeling approaches for assessing diagnostic error without a gold standard: with applications to p53 immunohistochemical assays in bladder tumors. 1141 91

The expression of p53, c-erbB-2, bcl-2 and c-myc proteins was compared to the quantity of the nucleolar organiser regions (AgNORs) and MIB-1 antigen to elucidate the relationship between oncogene expression and rapidity of cell proliferation and tumor growth fraction. Sections from 50 male breast carcinomas (MBC) and 62 superficial papillary bladder neoplasias were stained with the standardised AgNOR method and monoclonal antibodies MIB-1, DO7, CB11, bcl-2 124 and 9E11. p53 immunopositivity was associated with high AgNOR quantity and MIB-1 scores both in MBC and bladder neoplasm. c-erbB-2 expression was associated with high AgNOR quantity in bladder neoplasm. bcl-2 expression was associated with low AgNOR quantity in MBC. c-myc expression was associated with high AgNOR quantity in MBC. MBC patients with low AgNOR quantity, and p53, c-erbB-2 and c-myc immunonegativity had the longest overall survival. Patients with bladder neoplasia with low AgNOR quantity, negative p53 and positive c-erbB-2 immunostaining had the longest disease-free survival time. Our results indicate that p53 overexpression reflects both the rapidity of cell proliferation, as assessed by AgNOR quantity, and tumor growth fraction, as assessed by MIB-1 scores, while c-erbB-2, c-myc and bcl-2 expression mainly reflects the rapidity of cell proliferation. The combination of AgNOR quantity and oncogene expression may stratify patients into different risk groups.
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PMID:Relationship between AgNORs, MIB-1 and oncogene expression in male breast carcinoma and papillary superficial bladder neoplasm. 1288 2