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)

Skin lesions induced by exposure of three strains of female hairless mice to the light emitted by uncovered halogen quartz lamps were subjected to histopathological analysis. We examined 170 representative specimens out of a total of 597 skin lesions, i.e. 38 out of 74 SKH-1 mice, 110 out of 472 MF-1 mice, and 42 out of 51 C3H mice. The results provided evidence of various types of alterations, including preneoplastic changes, such as epidermal hyperplasia, and benign tumours, such as papillomas, as well as tumours with an increasing degree of malignancy, i.e., keratoacanthoma-like tumours, appendage/basal tumours, actinic keratoses/carcinomas in situ, and squamocellular carcinomas. SKH-1 was the most sensitive strain to the far-ultraviolet wavelengths delivered by halogen lamps, as shown not only by the shortest latency time and the highest multiplicity of skin lesions but also by the highest frequency of malignant tumours. Some areas of atypical melanocyte proliferation were only detected in C3H pigmented mice. Eighty-two of the lesions excised from MF-1 mice were additionally examined for p53 protein by immunohistochemical methods. Formalin-fixed, paraffin-embedded sections and frozen sections were analyzed in parallel by using polyclonal CM-1 antibody and monoclonal PAb240 antibody, respectively. A positive response for p53 was only observed in squamocellular carcinomas, and was related to the size of cancers; in fact, six out of 10 cancers of 10-30 mm in diameter were positive, whereas all 16 cancers of 2-9 mm in diameter were negative. All six positive squamocellular carcinomas were detected by using the CM-1 antibody, which recognizes both wild-type and mutant forms of p53 protein, and five of them were also positive with the PAb 240 antibody, which only recognizes the mutant form. Thus, p53 mutation appears to be a late event in the development of halogen-induced skin tumours in hairless mice, requiring a severe degree of malignancy and an advanced stage of the neoplastic mass growth.
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PMID:Detection of p53 and histopathological classification of skin tumours induced by halogen lamps in hairless mice. 798 4

Immunohistochemical demonstration of p53 is thought to reflect mutations of the p53 gene. Although p53 expression or mutation has been investigated in a variety of carcinomas, it has not been examined in intrahepatic cholangiocarcinoma (CC). We investigated expression of p53 in formalin-fixed, paraffin-embedded archival specimens of 40 CCs (22 autopsy cases and 18 surgical cases) by immunohistochemistry using four antibodies (PAb1801, DO-7, BP53-12, CM1). We also attempted to enhance p53 expression by pretreatments of tissue sections by pepsin digestion as well as by microwave oven heating. Formalin-fixed, paraffin-embedded archival surgical specimens of 15 colon carcinomas were used as controls. In surgical cases, p53 expression was abolished by pepsin predigestion, although it was greatly enhanced by pretreatment of microwave oven heating in all immunostainings (PAb1801, DO-7, BP53-12, CM1). In surgical cases immunostained with microwave oven heating, DO-7, BP53-12, and CM1 showed frequent p53 expression (22% in CC; 60-67% in colon carcinoma), whereas PAb1801 showed low p53 expression (0% in CC; 13% in colon carcinoma). In contrast to the surgical cases, all 22 CCs of autopsy cases showed no p53 expression by any antibodies as well as by any pretreatments. These results shows that a pretreatment of tissue sections by microwave oven heating is a very good method for demonstrating p53 protein in formalin-fixed, paraffin-embedded archival materials and that DO-7, BP53-12, and CM1 are useful antibodies for detection of p53 in formalin-fixed, paraffin-embedded archival materials. No expression of p53 in autopsy cases of CC suggests that p53 antigenicity is lost during autopsy procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methods in pathology. p53 expression in formalin-fixed, paraffin-embedded archival specimens of intrahepatic cholangiocarcinoma: retrieval of p53 antigenicity by microwave oven heating of tissue sections. 800 49

Using immunohistochemical methods, we analyzed the association between nuclear p53 overexpression and various clinicopathological parameters in patients with endometrial cancers. Formalin-fixed and paraffin-embedded tissue sections from 139 cases of endometrial cancer (endometrioid type, 126; serous papillary type, 12; and clear-cell type, 1) were stained with anti-p53 monoclonal antibody (MAb) DO7. Overexpression of p53 was associated with high malignant potential, including extensive muscular invasion, advanced surgical stage, high histological grade, serous papillary type and a personal history of cancer. Lymph-node metastasis was also related to p53 overexpression with marginal significance. Survival curves determined by the Kaplan-Meier method and univariate analysis showed p53 overexpression to be associated with a poor outcome in endometrial cancer patients. However, multivariate analysis using the stepwise Cox proportional-hazard model showed that whereas lymph-node metastasis, a personal history of cancer and muscular invasion were related to poor survival rates, p53 overexpression was not. Consequently, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial cancer, although a still larger sample of patient material would be required to assess this issue definitively.
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PMID:Clinicopathological characteristics of p53 overexpression in endometrial cancers. 801 10

Cell lines derived from formaldehyde-induced nasal tumors in Fischer 344 rats were established. All of the lines were found to be epithelial and aneuploid and to express keratin, transforming growth factor-alpha, and epidermal growth factor receptor transcripts. Two of four lines were tumorigenic upon injection into nude mice, and these lines also contained point mutations in the p53 suppressor gene. The data indicate that these lines possess characteristics that make them a valuable tool for the study of chemically induced respiratory tract carcinogenesis.
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PMID:Characterization of cell lines derived from formaldehyde-induced nasal tumors in rats. 814 52

Formalin-fixed, paraffin-embedded surgical specimens from 137 primary central nervous system tumors, including 26 astrocytomas (21 fibrillary, 1 protoplasmic, 1 gemistocytic and 3 pilocytic), 26 anaplastic astrocytomas, 9 glioblastomas, 1 gliosarcoma, 8 oligodendrogliomas, 4 ependymomas, 1 anaplastic ependymoma, 2 subependymomas, 3 paragangliomas, and 57 meningiomas, were immunostained with the CM1 polyclonal (pAb) and the DO-7 monoclonal (mAb) antibodies against the p53 protein, using the streptavidin/peroxidase method. In addition, two series of 17 and 9 medulloblastomas were also immunostained with the above pAb and mAb, respectively. p53 protein expression was observed in 7 fibrillary astrocytomas, 17 anaplastic astrocytomas, 5 glioblastomas, 1 gliosarcoma, 1 oligodendroglioma, 1 anaplastic ependymoma, and 4 meningiomas with the CM1 pAb. An additional 10 cases (i.e., 3 anaplastic astrocytomas and 7 meningiomas) were found to be p53 protein positive with the DO-7 mAb. Of the medulloblastomas, 8 (of the 17) and 4 (of the 9) were found to express p53 protein with CM1 pAb and DO-7 mAb, respectively. Our results indicate that p53 protein is expressed in a number of central nervous system neoplasms, and suggest that in astrocytic tumors a possible association may exist between p53 protein expression and tumor progression through increasing histological grades of malignancy.
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PMID:p53 protein expression in central nervous system tumors: an immunohistochemical study with CM1 polyvalent and DO-7 monoclonal antibodies. 833 39

Formalin-fixed, paraffin-embedded biopsies of 193 women with primary breast cancer followed-up for over 10 years were analysed immunohistochemically for the expression of p53 protein. Altogether, 58% (113/193) of the tumors were positive for p53 protein. Over-expression of p53 was associated with the ductal type, high-grade tumors, dense stromal inflammatory cell infiltrate, high S-phase fraction, high mitotic frequency and high values of the nuclear factors. In univariate analysis, intense p53 over-expression predicted a poor outcome, whereas a short recurrence-free survival (RFS) was related to p53 negativity. In axillary lymph-node-negative (ANN) tumors, p53 negativity was related to short RFS, and in axillary lymph-node-positive (ANP) tumors this inverse relationship was statistically significant. In Cox's analysis, p53 protein over-expression had no independent prognostic value comparable with the well-established prognostic factors. However, p53 protein accumulation was an independent indicator of long RFS in the entire cohort, in ANP tumors and in rapidly proliferating tumors. The results indicate a dual role for p53 protein over-expression in breast cancer prognosis. The low survival probability associated with intensively p53-positive tumors is probably related to rapid cancer-cell proliferation, whereas the long RFS of p53-positive tumors might be explained by the development of circulating antibodies to p53 protein. The role of p53 protein in breast cancer is incompletely understood, and the p53 gene should be subjected to detailed analysis of specific mutations.
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PMID:p53 protein expression in breast cancer as related to histopathological characteristics and prognosis. 834 53

Striking differences were found between different histological types of breast cancer when 263 invasive breast carcinomas were tested for nuclear p53 accumulation in formaldehyde-fixed paraffin sections. Nuclear p53 accumulation was found in > 10% of tumor cells in 61% of medullary carcinomas (22/36), 37% of grade 3 ductal not otherwise specified carcinomas (32/86), 4% of lobular carcinomas (2/47), and 0% (0/7) of mucinous carcinomas. Strong cytoplasmic p53 staining was noted in 32% of lobular carcinomas. High percentages of medullary and high-grade ductal breast carcinomas accumulate nuclear p53, but these tumors have favorable and poor prognoses, respectively. Thus, whereas nuclear p53 accumulation can be associated in these tumors with high morphological malignancy grades in general and with tumor cell proliferation in particular, p53 accumulation is not necessarily correlated with biological aggressiveness. Overall incidence of p53-positive tumors in a particular series of breast carcinomas (in our study 28%) will depend on the ratio of ductal not otherwise specified, medullary, and lobular carcinomas.
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PMID:Nuclear p53 protein accumulates preferentially in medullary and high-grade ductal but rarely in lobular breast carcinomas. 829 10

Physiologic overexpression of p53 protein may occur in the G1 stage of the cell cycle to slow down the cell cycle and allow DNA repair in stressed or injured cells. We questioned whether there is increased expression of p53 protein in acutely inflamed mucosa (AI) and regenerated mucosa (RM) in ulcerative colitis (UC) and Crohn's disease (CD). Formalin-fixed paraffin-embedded sections of resected bowels from eight patients with UC and 20 with CD were reviewed, and blocks were selected having areas defined as follows: AI = two high-power fields (HPFs) at the edge of an ulcer, or one HPF with an inflamed crypt in the center; RM = branched or irregular glands with only mild chronic inflammation. Blocks with normal mucosa were available in 20 cases. One case of CD also had dysplasia, adenoma, and invasive carcinoma. p53 was identified with PAb1801 antibody using a labeled avidin-biotin immunoperoxidase technique. In each defined area, the positive nuclei were counted and expressed as the number of positive nuclei per 10 HPFs. Data were analyzed statistically for comparisons within and between the diseases. In normal mucosa, only rare cells expressed p53 in two cases of CD. The mean frequency of positive nuclei was 2.24/10 HPFs in AI and 0.30/10 HPFs in RM in CD, and 7.63/10 HPFs in AI and 1.14/10 HPFs in RM in UC. Differences between the means for AI and RM were statistically significant in both UC and CD. Although not significant, the frequency of positive staining in both AI and RM was greater in UC as compared with CD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of p53 antigen in inflamed and regenerated mucosa in ulcerative colitis and Crohn's disease. 853

In the present study the prognostic significance of accumulation of nuclear p53 protein on survival and freedom from local progression was investigated. Formalin-fixed, paraffin-embedded sections obtained by bronchoscopy or mediastinoscopy were used to examine the expression of nuclear p53 protein using immunohistochemistry. In 37 cases (57%), overexpression of the p53 protein was detected. No relation was found between p53 expression and other pretreatment variables. Response to radiotherapy was found in 11 p53-negative cases (65%) versus 10 p53-positive cases (42%). Freedom from local progression was significantly better in the p53-negative cases as compared with the p53-positive cases. The p53-negative cases who responded to radiotherapy showed an excellent freedom from local progression rate after 2 years of 100%, whereas all p53-positive cases without response to radiotherapy showed local progression within 24 months. Overall survival between p53-negative and -positive cases did not differ, however the disease-specific survival was found to be worse in the p53-positive cases as compared to the negative cases (median survival 8.4 vs. 14.4 months (P < 0.05)). No correlation was found between p53 expression and the frequency of distant metastases. In conclusion, the results of this study suggest that p53 protein expression may be of prognostic value on freedom from local progression in non-small cell lung carcinoma.
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PMID:The prognostic significance of accumulation of p53 protein in stage III non-small cell lung cancer treated by radiotherapy. 853 9

Alterations in the tumor-suppressor gene p53 are common in many types of human malignancies, but the potential role of p53 in the pathogenesis of cutaneous melanoma is controversial. The gene product, p53 protein, is normally present in very small amounts in noncancerous tissues. Missense mutations lead to accumulation of mutant p53 in the cells, which makes it detectable immunohistochemically in many cancers. Formalin-fixed, paraffin-embedded sections of 14 primary invasive melanomas, 3 cutaneous melanoma metastases, and 10 predominantly intradermal melanocytic nevi were reacted with a panel of three anti-p53 monoclonal antibodies (mAbs) (PAb240, PAb1801, and DO7) and a mAb against Ki-67 (MIB-1), a marker of cellular proliferation. p53 was not detected in morphologically normal epidermal melanocytes or nevus cells. A single primary invasive melanoma, having a very high index of proliferation (Ki-67 expression in > 50% of cells), had diffuse nuclear labeling with all three anti-p53 mAbs used. Abnormalities of p53 expression occur rarely in cutaneous melanomas, but overexpression of p53 may occur in a subset of melanomas with a high index of proliferation.
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PMID:p53 expression is rare in cutaneous melanomas. 860 Jul 97


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