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)

Formaldehyde induces squamous cell carcinomas in the nasal passages of rats following chronic inhalation exposure at concentrations of > or = 10 ppm. We have examined the complementary DNA of the tumor suppressor gene p53 from 11 primary formaldehyde-induced tumors for mutation using DNA sequence analysis. A polymerase chain reaction-amplified fragment of the rat p53 complementary DNA containing the evolutionarily conserved regions II-V was directly sequenced from each tumor. Point mutations in the p53 complementary DNA sequence were found in 5 of 11 of the tumors analyzed. These data demonstrate p53 point mutations in formaldehyde-induced squamous cell carcinomas and indicate a common alteration in certain rat and human squamous cell carcinomas of the respiratory tract.
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PMID:p53 mutations in formaldehyde-induced nasal squamous cell carcinomas in rats. 139 39

We have analyzed the expression of the p53 tumor suppressor gene in paraffin-embedded sections of normal and malignant head and neck and lung tumors by immunohistochemistry using the PAb 1801 monoclonal antibody (MAb). The PAb 1801 does not consistently detect its p53 epitope in tissue fixed in 10% buffered formaldehyde. However, the antibody is effective in AMeX-fixed specimens, thereby permitting the improved morphologic localization of p53 phosphoprotein in paraffin embedded tissue. Of 33 primary head and neck carcinomas analyzed from AMeX-fixed, paraffin-embedded sections, 21 (64%) showed heterogeneous staining with PAb 1801. All 33 normal samples of head and neck tissues were negative. Similarly, 13 out of 20 lung carcinomas (65%) showed heterogeneous staining while none of normal lung tissues were positive. The data indicate a strong positive correlation between p53 detection by PAb 1801 and carcinomas of the head and neck and of lung. However, there was no obvious correlation between p53 staining and the number of involved nodes, the stage of disease or the degree of differentiation in these carcinomas.
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PMID:Improved immunohistochemical detection of p53 protein in paraffin--embedded tissues reveals elevated levels in most head and neck and lung carcinomas: correlation with clinicopathological parameters. 144 95

The tumor suppressor protein, p53, protects somatic cells against the accumulation of genomic alterations. Cells harboring mutant or inactivated wild-type p53 protein are at risk for the development of genomic instability. Nuclear accumulation of p53 protein is associated with the stepwise dedifferentiation of papillary carcinoma. We asked whether nuclear p53 accumulation is associated with two known indicators of poor prognosis in papillary carcinoma. We studied 55 consecutive papillary cancers (28 from Russia, and 27 from upstate New York). Nuclear p53 immunoreactivity was assessed using a monoclonal antibody, DO-1, on Formalin-fixed paraffin-embedded specimens. The DNA index was determined by computerized image analysis of Feulgen-stained sections. Nearly all cases were well differentiated and none were associated with distant metastases or extrathyroidal invasion. All primary lesions were less than 4 cm in diameter, and almost all patients were female. Nuclear p53 immunoreactivity was associated with a high-risk group characterized by two known indicators of poor prognosis: age > 50, aneuploid DNA content, or both. In the high-risk group (N = 24) 33% of cases displayed nuclear p53 positivity, compared with only 6% in a low-risk group (N = 31) which lacked both features (P = 0.015, two-tailed Fisher exact test). Nuclear accumulation of immunoreactive p53 protein is associated with two established indicators of poor prognosis in papillary carcinoma of the thyroid. This result is consistent with the idea that aberrations in p53 function are associated with the stepwise loss of differentiation in this cancer.
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PMID:Nuclear p53 immunoreactivity in papillary thyroid cancers is associated with two established indicators of poor prognosis. 755 91

Immunohistochemically detectable levels of p53 may be seen early in the malignant transformation of some neoplasms. To determine if p53 is immunocytochemically detectable, and therefore presumptively abnormal, in oral dysplasias and in situ carcinomas, and to explore the natural history of p53 protein expression in these lesions, sequential biopsies from patients with lesions occurring in the same anatomic site were examined. Formalin-fixed, paraffin-embedded sections from 19 patients were evaluated immunohistochemically for p53 protein using antibody clones Pab1801 and BP53-12. With two exceptions, comparable results were observed with these antibodies. p53 protein was detected immunocytochemically in 6 of 13 patients with dysplasias; 3 of these progressed to p53-positive invasive carcinoma, one advanced to a more severe grade of p53-positive dysplasia, one developed into a p53-negative verrucous carcinoma, and one represented a p53-positive dysplasia developing five years after treatment of a p53-positive carcinoma. The p53-positive dysplasias, which were found in all subtypes (mild, moderate, severe), preceded histologic malignant change by months to years. p53 detection was evident in 4 of 6 patients with in situ lesions. Sequential biopsies of three of these lesions showed no change in lesion histology or p53 staining, and one lesion advanced to a p53-positive carcinoma. It is concluded that p53 protein may be detected early in the development of a subset of p53-positive oral squamous cell carcinomas. This phenomenon may be seen in dysplasias and in situ lesions, and it may have prognostic implications.
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PMID:p53 protein expression in sequential biopsies of oral dysplasias and in situ carcinomas. 772 17

Mutation of the p53 tumor suppressor gene is a common event in many human cancers and has been specifically associated with invasive squamous cell carcinoma of the human skin and respiratory tract. Alterations in the p53 gene have also been identified in certain rodent tumors, including formaldehyde-induced nasal squamous cell carcinomas. Overexpression of transforming growth factor-alpha (TGF-alpha) is associated with carcinomas of the head and neck and respiratory tract in human patients and formaldehyde-induced rat nasal squamous cell carcinomas. Sections of rat noses containing tumors and other formaldehyde-induced lesions from rats exposed to 15 ppm formaldehyde vapor were examined using immunohistochemical techniques to detect and identify potential relationships between the presence and distribution of p53, proliferating cell nuclear antigen (PCNA), and TGF-alpha proteins. The five tumors that had p53 mutations were for mutant p53 protein by immunohistochemistry and three of six tumors with no detected p53 mutations were also immunoreactive for p53 protein. The presence, pattern, and distribution of p53 staining in tissue sections depended on the morphology of the lesion. PCNA immunoreactivity was strikingly similar in pattern and distribution to p53 immunoreactivity. The pattern and distribution of immunoreactivity for TGF-alpha did not directly correlate with the other markers. Mutation of the p53 tumor suppressor gene may be an important step in the progression of formaldehyde-induced nasal carcinogenesis in the rat. This study demonstrated that immunohistochemistry is a useful tool for the identification of sites within tumors that might have p53 mutations.
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PMID:Immunohistochemical localization of p53, PCNA, and TGF-alpha proteins in formaldehyde-induced rat nasal squamous cell carcinomas. 774 82

We investigated the prognostic significance of p53 gene abnormalities and ras gene mutations in patients with curatively resected stage I lung adenocarcinoma. Formalin-fixed and paraffin-embedded tissues were obtained from 30 patients who had undergone curative resection for stage I lung adenocarcinoma. Abnormalities of the p53 gene were detected using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis and immunohistochemistry and ras mutations were detected using PCR-restriction fragment length polymorphism (RFLP) analysis. Both univariate and multivariate analyses were performed to assess the relationship between the presence of abnormalities of these genes and the patients' disease-free survival. Eleven tumors (37%) had mutated p53 sequences and 11 (37%) showed p53 overexpression. A total of 15 tumors (50%) had p53 gene abnormalities and the concordance rate was 73%. Seven tumors (23%) showed mutated ras sequences. The univariate analysis revealed that the disease-free survival of patients with any p53 abnormality was shorter than that of those without abnormalities (P = 0.02, generalized Wilcoxon test), and survival of those with p53 protein overexpression was more significantly shorter (P = 0.003, generalized Wilcoxon test). Multivariate analysis using the Cox proportional hazards model indicated that the presence of p53 abnormalities was a significantly (P = 0.01) unfavorable prognostic factor. There was no significant correlation between the presence of ras mutation and survival. These results suggest that analysis of the p53 gene may be helpful for the selection of high-risk patients for clinical trials of adjuvant therapy for stage I lung adenocarcinoma.
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PMID:Prognostic significance of p53 and ras gene abnormalities in lung adenocarcinoma patients with stage I disease after curative resection. 785 88

A significant black/white difference in breast cancer prognosis has been observed in the United States. Alterations of p53 tumor suppressor gene in breast cancer have been associated with poor prognosis. This study was designed to test the hypothesis that p53 gene alterations are related to the difference in prognosis between black and white breast cancer patients. Formalin-fixed paraffin-embedded breast tissue blocks were available from 45 black and 47 white patients for PCR-single strand conformation polymorphism analysis and DNA sequencing. The types of p53 gene alterations were compared between blacks and whites. Associations between p53 gene alterations and survival were also evaluated. Three missense, 2 nonsense, 1 microdeletion, 1 intron, and 4 silent mutations were detected in blacks, while 7 missense, 1 microdeletion, 1 silent mutation, and 3 polymorphisms were observed in whites. Among the point mutations, G:C to A:T transitions at non-CpG sites were found in 80.0% of blacks (8 of 10) and 62.5% of whites (5 of 8). Significantly poorer survival associated with p53 gene alterations was observed for blacks (P = 0.012), but not for whites. Black patients with p53 alterations had a significant 4-5-fold excess risk of death from breast cancer than those without p53 alterations. Adjustment for stage, age, tumor histopathology, receptor status, and adjuvant treatment did not change the excess risk. The findings suggest that the types of p53 gene alterations may contribute to the racial difference in breast cancer survival.
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PMID:Racial disparity in the association of p53 gene alterations with breast cancer survival. 788 57

The aim of this study was to gain some insight into the relationship of human papillomavirus (HPV) infection to p53 expression and to some pathological parameters in precancerous lesions of the larynx. Formalin-fixed paraffin-embedded tissue sections containing human laryngeal precancerous lesions were screened for p53 protein by immunohistochemistry with the monoclonal antibody DO7 and for the presence of HPV infection by polymerase chain reaction with consensus primers directed against the E6 gene. The presence of p53 protein was detected in 31 of 57 specimens (54.4%) including 7 of 9 cases with mild dysplasia (78%), in 4 of 9 cases with moderate dysplasia (44%), and in 15 of 23 cases with severe dysplasia (65%). Of 16 samples with keratotic benign squamous metaplasia, 5 were also p53 positive (31%). Of 6 samples that were HPV positive, all were of type 16. Interestingly, 3 of the 6 HPV-positive samples were p53 negative. There was 1 HPV-positive case with strong p53 staining and 2 HPV-positive cases with minimal p53 staining. The 2 HPV-positive cases with minimal p53 staining had mild dysplasia. The HPV-positive case with strong p53 staining displayed severe dysplasia. Of 23 cases that were both HPV and p53 negative, 11 presented with keratosis and no dysplasia, 5 with moderate dysplasia, and 7 with severe dysplasia. Our data indicate that nuclear accumulation of p53 protein, presumably resulting from p53 gene mutation, may occur in HPV-infected epithelial tissues. On the other hand, there are many precancer lesions, some exhibiting moderate or severe dysplasia, that are both HPV negative and p53 unreactive, suggesting that alterations of genes other than the E6 oncogene and the p53 tumor suppressor gene play a role in early laryngeal carcinogenesis.
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PMID:Expression of p53 protein related to the presence of human papillomavirus infection in precancer lesions of the larynx. 788 42

Cell proliferative activity and the overaccumulation of P53 suppressor gene were evaluated in 26 cases of gestational trophoblastic disease and five cases with normal placentae. Formalin-fixed, paraffin-embedded histological sections were used for immunohistochemistry, utilizing the avidin-biotin-peroxidase technique and antibodies to PCNA (proliferative cell nuclear antigen) and to P53 (product of suppressor gene). Positive reactions for PCNA were graded from 1+ to 3+ (1(+)-less than 10% of cells; 2(+)-10-50%; 3(+)-more than 50%). Eight of 10 cases of choriocarcinoma (80%) showed moderate to strong reactivity for PCNA (2+ and 3+). All 9 cases with hydatidiform mole and 6 of 7 cases with partial mole also demonstrated 2+ and 3+ reactions for PCNA. There was minimal or no PCNA staining in the trophoblastic cells of normal placentae. Five of 10 cases with choriocarcinoma (50%) exhibited P53 overaccumulation as did 7 of 9 cases with hydatidiform mole (78%). In hydatidiform moles, P53 staining was limited to the areas of trophoblastic proliferation separate from chorionic villi. None of the partial moles or normal placentae showed P53 overaccumulation. It is concluded that the cell proliferative activity of choriocarcinomas as well as complete and partial hydatidiform moles are comparable. On the other hand, the mutation of P53 suppressor gene, as demonstrated by the overaccumulation of P53 protein, is seen only in true trophoblastic neoplasms, namely, choriocarcinomas and hydatidiform moles.
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PMID:Cell proliferative activity and mutation of P53 suppressor gene in human gestational trophoblastic disease. 790 85

This article summarizes the most recent developments and current practice of immunohistochemistry in the diagnosis of hematologic malignancy. Increased availability of monoclonal antibodies applicable in formaldehyde-fixed and paraffin-embedded tissue is discussed as are immunohistochemical definitions for many small cell lymphoma entities. Evaluation is made of the biologic potential of lymphomas and leukemias by the use of antibodies to proliferation antigens, such as Ki-67 and products of tumor suppressor genes (p53).
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PMID:Immunohistochemical evaluation of hematologic malignancies. 796 Dec 86


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