Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohistochemically in matched normal urothelium, dysplasia and cancer specimens selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartment, while in moderate and severe dysplasia its expression was detectable also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein showed a increasing trend toward the progression of bladder tumorigenesis (P < 0.01) and a significant reciprocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2 expression was more frequently observed in superficial (P < 0.02) or low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for both bcl-2 and p53 in cancer lesions had a significantly more favorable prognosis compared with those with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis and to enhance tumor aggression in some extent.
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PMID:Reciprocal expression of bcl-2 and p53 oncoproteins in urothelial dysplasia and carcinoma of the urinary bladder. 975 96

Although almost all pituitary tumors are benign adenomas, a surprisingly large number of these tumors invade tissues outside of the pituitary gland. Such invasion, by itself, is not diagnostic of pituitary carcinomas, which are exceedingly rare (0.13% of 2,342 pituitary tumors in one series). Several different criteria are available to determine whether a tumor is invasive. Intraoperative biopsies demonstrate an 85% incidence of microscopic invasion of the dura. Evidence of gross invasion at surgery and radiologic evidence of invasion on magnetic resonance imaging (MRI) and computed tomographic (CT) scans occur at a much lower incidence but may be more predictive of surgical cure. Invasive adenomas also have higher proliferation rates than do noninvasive adenomas, as shown by immunohistochemical detection of proliferating cell nuclear antigen (PCNA), Ki-67, and MIB-1. The expression of p53, increased epidermal growth factor receptors, and protein kinase C activity also correlate with invasion and aggressive behavior. Clinically significant invasion is more frequent with macroadenomas. Macroadenomas of all pituitary tumor subtypes except gonadotroph macroadenomas have a greater than 50% incidence of gross invasion. Currently, there is no accepted means of predicting an adenoma's clinically significant invasiveness and long-term aggressiveness.
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PMID:Aggressive pituitary tumors. 977 77

Apoptosis is a key phenomenon in the regulation of the life span of terminally differentiated leukocytes. Human gingiva represents an established model to study immune responses to bacterial infection. In this investigation, we used the TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) technique to evaluate presence and topographic location of apoptosis-associated DNA damage in human gingival biopsies along with the expression of the p53 and Bcl-2 apoptosis-regulating proteins. Qualitative data analysis showed high densities of cells expressing DNA damage and p53 both within the epithelial attachment to the tooth and in the perivascular infiltrate (infiltrated connective tissue [ICT]) immediately underlying the site of chronic bacterial aggression. Topographic consistency between DNA damage- and p53-positive cells was consistently observed. Quantitative analysis of the ICT showed mean densities of DNA damage- and p53-positive cells of 345 +/- 278 and 403 +/- 182 cells/mm2, respectively. Numerical consistency was confirmed by multivariate regression analysis: densities of DNA damage-positive cells were significantly predicted by densities of p53-positive cells (P = 0. 001, r2 = 0.84). In the ICT, cells displaying biotinylated DNA nicks were 3.8% +/- 2.7% of total cellularity, while p53- and Bcl-2-positive cells represented 4.4% +/- 1.7% and 15.4% +/- 6.7% of total cells, respectively. It is suggested that p53 expression associated with DNA damage is a prevalent phenomenon in chronically inflamed human gingiva, and that apoptosis may be a relevant process for the maintenance of local immune homeostasis at sites of chronic bacterial challenge in vivo.
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PMID:In situ detection of apoptosis at sites of chronic bacterially induced inflammation in human gingiva. 978 21

Proliferation markers are widely used as indicators of tumour progression and aggression. Fixation and antigen retrieval methods may enhance the immunocytochemical sensitivity of these markers but may also lead to loss of specificity. As these methods are often used quantitatively, standardisation of internal and external methodology is paramount. This study aimed to compare the effects of alcohol and formalin fixation and of microwaving on the immunocytochemical demonstration of p53, PCNA and Ki-67 in oral squamous cell carcinoma using duplicate tissue blocks from 24 cases. Both qualitative and quantitative differences in antigen expression were revealed. Whilst alcohol fixation alone at least maintained and usually increased the strength of positive staining, microwaving alcohol-fixed sections often gave rise to non-specific staining. p53 staining following microwave enhancement of alcohol-fixed tissue showed a significant incidence of conversion of negative results to positive and of positive staining in unexpected tissue components. Alcohol fixation increased the sensitivity of PCNA detection with a far less dramatic loss of specificity. The results emphasise the need for careful standardisation of immunocytochemical methods, particularly when used quantitatively and for inter-laboratory comparisons.
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PMID:p53, PCNA and Ki-67 expression in oral squamous cell carcinomas: the vagaries of fixation and microwave enhancement of immunocytochemistry. 979 97

Well-documented cases of malignant degeneration in pleomorphic xanthoastrocytoma and of anaplastic pleomorphic xanthoastrocytoma are rare in the literature. We report 2 cases of pleomorphic xanthoastrocytoma, 1 of which demonstrated clear evidence of malignant degeneration in the absence of prior radiation therapy over an 18-year period. Both anaplastic tumors were characterized by foci of necrosis and increased mitotic activity (3 and 2 mitotic figures/10 high-power fields). Both tumors demonstrated focal positive staining for glial fibrillary acidic protein and showed marked reticulin deposition. An MIB-1 labeling index (marker of cell proliferation) in the initial low-grade-appearing tumor in case 1 was 0.1%. The recurrent tumor in case 1 had an MIB-1 labeling index of 4.9%, and the anaplastic tumor in case 2 had an MIB-1 labeling index of 5.4%. Significant cyclin D1 immunoreactivity was not observed in either anaplastic tumor. Two percent to 3% of tumor cells stained positive with p53 protein antibody in the recurrent anaplastic tumor in case 1. Although histology may not reliably predict aggressive behavior in pleomorphic xanthoastrocytomas, the presence of increased mitosis, necrosis, and increased cell proliferation labeling indices may be indicative of a higher grade tumor.
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PMID:Anaplastic pleomorphic xanthoastrocytoma. 987 Aug 56

We report a case of giant cell tumor of the manubrium with radiological evidence of aggressiveness. Few cases of giant cell tumor of the sternum have been published. Extensive surgery offers the best hopes of recovery. Cytogenetic studies evidenced several clonal abnormalities including a 17q isochromosome. The TP53 suppressor gene is located at 17q13.1. Whether loss of one of the TP53 alleles may have contributed to the aggressive behavior of our patient's tumor is discussed.
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PMID:Giant cell tumor of the sternum. Report of a case with a 17q isochromosome. 1003

Inflammatory myofibroblastic tumors (IMTs) are uncommon spindle cell proliferations that occur in the viscera and soft tissue of children and young adults. Their biologic potential is indeterminate: 25% of IMTs recur, and rare examples undergo malignant transformation (MT). This study investigates histologic features, DNA ploidy, and expression of apoptotic regulatory and oncogenic proteins in IMTs in an attempt to identify those deviances that might correlate with aggressive behavior or MT. Twenty-four formalin-fixed, paraffin-embedded IMTs for which clinical outcome was known were evaluated for cellularity, cytologic atypia, mitoses, ganglion-like cells, inflammatory infiltrate, DNA ploidy by flow cytometric examination, and bax, bcl-2, p53, and c-myc expression by immunohistochemical analysis. Sixteen (67%) of the IMTs did not recur, 6 (25%) recurred, and 2 (8%) underwent MT. Cellular atypia was observed in 69% of the cases without recurrence, 100% with recurrence, and 100% with MT. Ganglion-like cells were present in 56, 100, and 100% of the IMTs without recurrence, with recurrence, and with MT, respectively. There was no difference in the degree of cellularity, mitoses, or inflammatory infiltrate among the outcome groups. All of the tumors expressed bax, and none expressed c-myc. Two (8%) were immunoreactive for p53, one of which recurred and one of which underwent MT. bcl-2 expression was observed in 9 (37%) of the IMTs, with no difference among the three groups. Two IMTs were aneuploid, one of which underwent MT. Neither morphologic evaluation for cellularity, mitosis, or inflammatory infiltrate nor expression of bax or c-myc were useful for prediction of clinical outcome. The combination of atypia, ganglion-like cells, p53 expression and DNA ploidy analysis, however, might be useful to identify IMTs that might undergo MT or pursue a more aggressive clinical course with recurrences.
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PMID:Comparison of DNA ploidy, histologic, and immunohistochemical findings with clinical outcome in inflammatory myofibroblastic tumors. 1010 13

Mantle-cell lymphoma (MCL) is a lymphoproliferative disorder derived from a subset of naive pregerminal center cells characterized by a nodular or diffuse proliferation of atypical lymphoid cells with a monoclonal B-cell phenotype and coexpression of CD5. Two cytologic variants have been identified, typical and blastic. Typical cases show a proliferation of small to intermediately sized lymphoid cells with irregular nuclei and scarce cytoplasm. Blastic variants include a spectrum of intermediate to large cells with round or irregular nuclei and finely dispersed chromatin. These cases have a higher proliferative activity and a more aggressive clinical evolution. MCL is genetically characterized by 11q13 translocations and bcl-1 rearrangement. This alteration leads to a constant overexpression of cyclin D1, which plays an important pathogenetic role, probably deregulating cell-cycle control by overcoming the suppressor effect of retinoblastoma protein (Rb) and p27Kip1. Detection of cyclin D1 may be used as a highly specific marker of MCL because it is expressed in virtually all of these tumors, but in only a few reported cases of aggressive variants of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and a small percentage of cases of multiple myeloma. Aggressive variants have additional genetic alterations, including inactivation of p53 and p16INK4a tumor-suppressor genes. Clinically, MCL presents in elderly males with advanced disease and frequent extranodal involvement, particularly with involvement of bone marrow, gastrointestinal tract, and spleen. The clinical evolution is relatively aggressive, with poor response to conventional therapeutic regimens and a median survival duration of 3 to 4 years. Further studies are needed to define better new therapeutic strategies for the management of these patients.
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PMID:Mantle-cell lymphoma. 1031 80

The transition of normal epithelium to invasive carcinoma occurs sequentially. In colorectal and cervical carcinogenesis, this transition is reflected by histomorphologically defined grades of increasing dysplasia that untreated may progress to invasive disease. In an attempt to understand the role of chromosomal aberrations during tumorigenesis we have applied comparative genomic hybridization using DNA extracted from defined stages of colorectal and cervical tumors, from low- and high-grade astrocytic tumors and from diploid and aneuploid breast carcinomas. Genetic instability, as measured by the number of chromosomal copy alterations per case, increases significantly at the transition from precursor lesions to invasive carcinomas and continues to increase with tumor stage. Aggressive tumors have a higher number of copy alterations per case. High-level copy number changes (amplifications) become more prevalent in advanced-stage disease. Subtractive karyograms of chromosomal gains and losses were used to map tumor stage-specific chromosomal aberrations and clearly showed that nonrandom chromosomal aberrations occur during disease progression. In colorectal and cervical tumors, chromosomal copy number changes were correlated with nuclear DNA content, proliferative activity, expression levels of the tumor suppressor gene TP53, and the cyclin-dependent kinase inhibitor p21/WAF1, as well as the presence of viral genomes. Here we summarize and review the results of this comprehensive phenotype/genotype correlation and discuss the relevance of stage-specific chromosomal aberrations with respect to diagnostic applications.
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PMID:Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation. 1037 65

The occurrence of distant metastases is the most feared manifestation of breast cancer, often occurring years after the primary surgery and associated with poor survival. The dominant metastatic clone is characterized by an accumulation of genetic alterations, but it is not actually known at what stage of the metastatic cascade these alterations have occurred. We investigated allelic losses during breast cancer progression in a series of 17 primary breast carcinomas and 22 corresponding brain, liver, lung, and bone metastases (mean metastasis-free interval, 31 months) by analyzing 19 microsatellite markers on seven breast cancer- or metastasis-related chromosomal regions and correlated the incidence of combined loss of heterozygosity (LOH) with metastasis-free and postmetastatic survival. We found that, in comparison with the corresponding primary tumor, additional LOH events are frequently found in metastases and that the incidence of combined LOH in the primary tumor, plus the occurrence of additional LOH events in the distant metastases, correlated significantly with decreased postmetastatic survival. Combined LOH of the three breast cancer-related chromosomal regions alone or in combination with allelic loss at the p53 gene region seems to have a specific influence on the aggressive behavior of metastases. We hypothesize that the occurrence of additional LOH events is either involved in termination of dormancy of micrometastatic tumor cells at distant organ sites or acquired during further progression of metastases.
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PMID:Loss of heterozygosity accumulation in primary breast carcinomas and additionally in corresponding distant metastases is associated with poor outcome. 1038 27


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