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

Cytofluorometric analysis of DNA content and immunohistochemical examination of p53 and PCNA were performed in colorectal adenomas, mainly borderline lesions, and cancers. Nuclear DNA content revealed aneuploidy and polyploid cells in severely atypical adenomas and cancers. Mutated p53 protein was also observed in severely atypical adenomas, especially tortuous and villous lesions and cancers. PCNA labeling index (P-I) was significantly increased in proportion to cell atypism and P-I over 50% was noted in half of severely atypical adenomas. Among infiltrating cancers, poorly differentiated adenocarcinoma showed high P-I. However, well differentiated adenocarcinoma infiltrating beyond the tunica muscularis propria showed various P-I values depending on the presence of metastasis to lymph node or blood vessel invasion. Furthermore, P-I in the metastatic lesion was significantly higher than that of primary lesion. These results suggest that severely atypical adenomas showing morphological features such as an increased N/C ratio, loss of polarity, roundish nucleus, tortuous and villous change of gland have malignant potentiality. So severely atypical adenomas have the clinical indication for polypectomy. In addition, poorly differentiated adenocarcinoma shows high proliferative ability and metastatic lesions or poorly differentiated components existing in infiltrating cancers may affect cancer development as productive clones.
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PMID:[Morphological atypism and clinicopathological factors in colorectal adenoma and cancer using nuclear DNA content, p53 and PCNA]. 782 98

The expression of C-myc p62, bcl-2, p53, PCNA and EBV-encoded LMP-1 proteins was studied by immunohistochemistry on paraffin-embedded skin specimens from 14 patients with early stage (premycotic erythema and second stage plaques) mycosis fungoides (MF), 21 patients with advanced stage MF (third stage plaques and tumors), 3 patients with Sezary's syndrome (SS) and 3 patients with pleomorphic medium and large cell cutaneous T-cell lymphomas (PML-CTCL). All 41 cases were also screened for the presence of EBV by using RNA in situ hybridization with EBER 1/2 oligonucleotides. Increased expression of C-myc p62, p53 and PCNA proteins was found in PML-CTCL and advanced stages of MF as compared to early stages of MF. These results suggest a relationship between levels of C-myc p62, p53 and PCNA proteins and aggressiveness of the cutaneous T-cell lymphomas. Furthermore, C-myc p62 and bcl-2 proteins were found to be frequently coexpressed in the present series. In view of the background information from in vitro findings and animal models that cooperation of C-myc and bcl-2 is important for lymphomagenesis, our results suggest that coexpression of these oncogenes may be implicated in the pathogenesis and/or the progression of cutaneous T-cell lymphomas. Neither LMP-1 expression nor EBV EBER l/2 transcripts were detected in our series suggesting that EBV is not involved in the pathogenesis of cutaneous T-cell lymphomas.
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PMID:Mycosis fungoides: expression of C-myc p62 p53, bcl-2 and PCNA proteins and absence of association with Epstein-Barr virus. 783 Nov 52

DNA ploidy (by image cytometry) and expression of proliferating cell nuclear antigen (PCNA) and p53 tumor suppressor gene product (by immunohistochemistry) were investigated in 15 cases of Hodgkin's disease (HD) and 12 cases of HD-like B-cell lymphoma (HD-like NHL). Reed-Sternberg (RS) cells and their variants were DNA aneuploid in all cases. However, the fraction of hyperoctaploid tumor cells was higher in HD than in HD-like NHL. PCNA expression was high in neoplastic cells (> 50%) and variable (5-40%) in reactive lymphocytes in both HD and HD-like NHL. p53 positivity was found in RS cells and their variants in 64% of HD cases, but only in 25% of cases of HD-like NHL. Our results support the suggestion that HD-like B-cell lymphomas should be considered as highly malignant non-Hodgkin's lymphomas rather than Hodgkin's disease.
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PMID:DNA content and expression of PCNA and p53 in Hodgkin's disease and Hodgkin's-like B-cell lymphoma. 783 7

Immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and p53 protein is important, particularly for the surgical diagnosis of neoplastic disorders. An effective, simple and reproducible method was established for observing the expression of these intranuclear antigens in routinely processed, formalin-fixed paraffin-embedded sections. Dramatic improvement of the antigenicity was obtained when the deparaffinized sections were heated in a hot water bath at 90 degrees C for 120 min in 0.01 mol/L citrate buffer, pH 6.0, for PCNA and in 0.01 mol/L phosphate-buffered saline, pH 7.2, for p53 protein. These reliable pretreatments are useful for the detailed comparative analysis of the expression of PCNA and p53 protein and fine histologic architecture and for retrospective study using a large number of archival specimens.
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PMID:Heat-induced antigen retrieval of proliferating cell nuclear antigen and p53 protein in formalin-fixed, paraffin-embedded sections. 783 77

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.
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PMID:Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. 783 39

An increasing body of evidence suggests that in addition to conventional histopathologic tumor characteristics, DNA content measurements, cell kinetic data, and investigations of tumor suppressor gene expressions might be of valuable information in breast cancer patients. Against this background we investigated immunohistochemically overexpression of the interphase associated protein proliferating cell nuclear antigen (PCNA) and the mutant p53 protein in routinely paraffin-embedded surgical specimens from 180 breast cancer patients with known nuclear DNA profiles. The mean clinical follow-up was 16 years (range 13-20 years). The percentage of PCNA immunoreactive tumor cell nuclei ranged between < 5% and 60% (mean 13.59 +/- 10.85%). There was a direct association between high levels of PCNA expression (> 20%) and p53 protein overexpression (p = 0.001), high histologic tumor grade (p = 0.009), and DNA aneuploidy (p = 0.019). Mutant p53 protein overexpression was found in 44 of 180 (24%) cases and was significantly related to high histologic tumor grade (p = 0.004), DNA aneuploidy (p = 0.001), and high levels of PCNA expression (p = 0.001). Patients with highly proliferative carcinomas (> 20% PCNA expression) had a shortened distant metastases-free survival when their neoplasms overexpressed p53. In contrast, the distant metastases-free survival of patients with highly proliferative, p53-negative tumors was significantly longer (p = 0.03). Immunohistochemical p53 protein overexpression thus appears to be indicative of an increased malignant potential in breast cancer patients. Highly proliferative tumors composed of p53 immunoreactive neoplastic cells clinically seem to behave more aggressively than the highly proliferative p53-negative tumors.
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PMID:Association of immunohistochemical p53 tumor suppressor gene protein overexpression with prognosis in highly proliferative human mammary adenocarcinomas. 784 4

Nuclear p53 immunoreactivity is demonstrated in infected oligodendroglia, as well as in a proportion of reactive and bizarre astrocytes, in seven progressive multifocal leukoencephalopathy (PML) biopsies. This likely represents binding to, and prolongation of the half-life of, wild-type p53 protein by JC virus T-antigen. Other possible mechanisms are considered. The same cells show proliferating cell nuclear antigen (PCNA) positivity, as do a proportion of morphologically normal oligodendroglia and astrocytes, reflecting proliferating populations of these glial sub-types. It is possible that functional inactivation of p53 in nonlytically infected astrocytes may allow neoplastic astrocyte clones to emerge. However, p53 and PCNA immunoreactivity per se cannot be regarded as indicative of neoplasia in PML, and caution must be exercised in the interpretation of such nuclear staining profiles.
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PMID:An immunohistochemical study of p53 and proliferating cell nuclear antigen expression in progressive multifocal leukoencephalopathy. 784 76

Karyomegalic interstitial nephritis was first described in 1979 by Mihatsch, who was reporting three such cases. We report here four additional cases as well as two family investigations. Our findings support the association of karyomegaly and interstitial nephritis as a distinct entity. Typical clinical features are asymptomatic progressive renal failure in the third decade of life and recurrent infections, mostly of the upper respiratory tract. Histologic alterations consist of markedly enlarged and hyperchromic nuclei in many tubular epithelial cells throughout the nephron accompanied by interstitial fibrosis in the surrounding atrophic tubules. Karyomegaly is not limited to the kidneys. In one case, autopsy revealed karyomegaly in epithelial and mesenchymal cells of many other organs. However, no association of karyomegaly with further histologic damage is evident except in the kidneys. Because of the familial clustering, karyomegalic interstitial nephritis seems to be an inherited disease. Examination of the nuclear proliferation-associated structures proliferating cell nuclear antigen/cyclin, Ki 67, and p53 suggests an inhibition of mitosis in karyomegalic cells. The finding of the same HLA haplotype, A9/B35, in four of six HLA-typed cases suggests the possibility of a genetic defect on chromosome 6, which is inherited and linked to the HLA locus.
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PMID:Karyomegalic interstitial nephritis: further support for a distinct entity and evidence for a genetic defect. 854 34

There is strong association of Barrett's oesophagus (BO) with adenocarcinoma. The sequence of events preceding malignancy appears to be reflux oesophagitis - ulceration - BO - dysplasia. One hundred and five biopsies of heterotopic columnar epithelium were stained for H&E, PAS/Alcian Blue and HID/Alcian Blue for the routine histology and neutral/acidic sialo- and sulphomucin staining. Other sections were silver impregnated by the Grimelius technique. Immunohistochemical techniques were applied for the assessment of the accumulation of p53 protein, "S" phase of the replication cell cycle using proliferating cell nuclear antigen (PCNA), marked for cell differentiation and proliferation using EGF and TGFa. 105 cases of heterotopic columnar epithelium consisted of 74 cases of BO, 25 junctional and 7 corpus mucosa. Dysplastic BO (n = 9) showed similar amount of sulphomucin and endocrine cell number when compared to non-dysplastic. PCNA study revealed a close similarity between dysplastic, indefinite for dysplasia and non-dysplastic, mucosal positive counts. Growth factors activity was significantly higher in dysplastic and indefinite than in non-dysplastic, but no such difference was found between dysplastic and indefinite for dysplasia BO. There was a significant concurrent p53 expression in dysplastic and indefinite for dysplasia BO. In conclusion, the practical utility of mucin stainings, endocrine cell count, assessment of cell proliferation and differentiation by PCNA, EGF and TGFa seems to be limited in differentiation of the dysplastic and indefinite for dysplasia BO. Altered expression of p53, particularly in combination with EGF and TGFa, may be useful in studying these lesions.
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PMID:Barrett's oesophagus: mucin composition, neuroendocrine cells, p53 protein, cellular proliferation and differentiation. 784 25

Mutant p53 expressed in many types of carcinoma lacks an inhibitory function on cell growth, but its role has been unclear. We performed two-parameter flow cytometry (FCM) to elucidate the relationship between the expression of p53 and the cell cycle in A431 cells. Fluorescence in situ hybridization proved that an A431 cell had two p53 genes whereas chromosome 17 was tetraploid. FCM showed that A431 cells expressed constantly high levels of p53 during the cell cycle. Under conditions of both serum deprivation and presence of hydroxyurea, p53 expression was decreased throughout the cell cycle, and the bivariate DNA/p53 distribution pattern during the cell cycle did not change. The expression of p53 was reduced to 60% for the first 4 h after the addition of cycloheximide, and showed no significant changes at least for 20 h. Treatment with Triton X-100 increased p53 immunoreactivity throughout the cell cycle. These results indicate that mutant p53 differs from proliferative markers such as PCNA, Ki-67 and DNA polymerase-alpha, and that there are no links between the expression of p53 and the cell cycle in A431 cells.
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PMID:Flow cytometric analysis of p53 expression during the cell cycle. 785 71


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