Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumour suppressor gene p53 is frequently mutated in neoplasia. Since mutant p53 protein is often over-expressed, mutation can be indirectly detected by immunocytochemical techniques. As microwave antigen retrieval is becoming a widespread method for increasing the antigenicity of paraffin sections, we investigated the application of this technique to p53 immunohistochemical staining of oral mucosa specimens. Paraffin sections of 22 squamous cell carcinomas (SCC) and 36 benign lesions were immunohistochemically stained with and without antigen retrieval. Without antigen retrieval p53 over-expression was observed in 6/22 SCC and 1/36 benign lesions. Following antigen retrieval positive staining was observed in 15/22 SCC and 35/36 benign lesions. Staining in benign lesions was confined to basal and parabasal cells and could reflect normal functioning of wild-type p53. We conclude that antigen retrieval increases the sensitivity of p53 immunoreactivity, but such staining is not specific for malignancy and should be interpreted with caution.
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PMID:The use of antigen retrieval for immunohistochemical detection of p53 over-expression in malignant and benign oral mucosa: a cautionary note. 866 57

Abnormalities in the p53 tumour suppressor gene and in the expression of its protein are common in colorectal carcinoma. The prognostic significance of these p53 abnormalities was studied in 66 patients with colorectal cancer, followed for more than 10 years. Single-strand conformation polymorphism (SSCP) analysis was used to detect alterations in exons 5-8 of the p53 gene. Paraffin sections were examined immunohistochemically for p53 overexpression with the monoclonal antibody DO-7 (Dako) both with and without microwave antigen retrieval. Abnormalities of the p53 gene were found in 41 per cent of cases by SSCP analysis. Outcome was unrelated to SSCP abnormalities (P = 0.19), except for the Dukes' A and B subgroup, where decreased survival was found in cases with abnormal SSCP (P = 0.01). Overexpression of p53 protein was seen by immunohistochemistry in 47 per cent of cases without, and in 52 per cent of cases with microwave antigen retrieval. Immunohistochemical overexpression of p53 protein either with or without microwave antigen retrieval was an independent prognostic indicator of poor survival. These results suggest that for routine purposes, immunohistochemical detection of the p53 protein product may be more useful than SSCP analysis of the encoding p53 gene in identifying those at high risk of colorectal cancer recurrence and death.
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PMID:Prognostic significance of p53 abnormalities in colorectal carcinoma detected by PCR-SSCP and immunohistochemical analysis. 901 55

The p53 gene is well known as a tumour suppressor gene. In addition, the mutated p53 gene is detected in a variety of human cancers including lung cancer, and is considered as an oncogene. Lung cancer is also frequently associated with interstitial lung diseases. Therefore, it may be possible to hypothesize that there might be some abnormality of p53 gene in interstitial lung diseases. This work examined the relationship between the p53 protein and gene in lung tissues of 28 patients with interstitial lung diseases. Among 28 patients, 13 cases were pathologically diagnosed to have usual interstitial pneumonia (UIP), 12 cases were diagnosed as having collagen vascular lung diseases, and three cases were diagnosed to have a non-specific interstitial pneumonia. Twenty-three tissue samples were obtained by open lung biopsy and five samples were taken by autopsy. Paraffin-embedded tissues were treated by microwave, and stained with an anti-p53 antibody (DO7) by the Avidin-Biotin-Peroxidase (ABC) method. In selected patients, mutations in exons 5-8 of the p53 gene were also examined by single-strand conformation polymorphism (SSCP) analysis and DNA sequence. In addition, the presence of anti-p53 antibodies in patients' sera was screened for by ELISA. Fifteen samples (53.6%) revealed overexpression of the p53 protein in the nuclei of alveolar epithelial cells. However, SSCP or sequence analysis, which was performed in 13 tissues, showed no mutations in exons 5-8 of the p53 gene. In conclusion, p53 proteins were overexpressed in interstitial lung diseases, and the expressed p53 protein was considered to be wild-type. This wild-type p53 protein may play a role in blocking the transformation of proliferative epithelial cells.
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PMID:Overexpression of p53 protein in interstitial lung diseases. 961 10

The aim of this study was to study the protein expression of six proto-oncogenes (epidermal growth factor receptor (EGFR), c-fms, c-myc, c-kit, c-erbB-2 and pan-ras) and one tumour suppressor gene (TP53), by immunohistochemical staining of normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia (CIN). Paraffin sections of 45 normal cervical specimens, 38 CIN grade one (CIN1), 37 CIN2 and 43 CIN3 were studied. An immunohistochemical (IHC) score was derived from the intensity of staining and the percentages of cells stained. In normal cervical specimens, a higher IHC score was found with EGFR and c-fms in superficial (S), intermediate (I) and parabasal (PB) cells compared with basal cells. In contrast, a higher IHC score was found with c-erbB-2 in basal cells in normal cervical specimens. Dysplastic cells in CIN had a higher IHC score with c-myc and c-erbB-2 than normal S/I and PB cells. Dysplastic cells had a higher score with EGFR than normal basal cells. However, a higher IHC score with EGFR and c-fms was found in normal S/I cells than dysplastic cells. These findings suggested that EGFR and c-fms were activated in more differentiated normal cells but were less active in less differentiated normal basal cells. However, EGFR was reactivated in dysplastic cells. Meanwhile, c-erbB-2 was activated in less differentiated normal basal cells and dysplastic cells, and was less active in differentiated normal cells. c-myc was activated in dysplastic cells. c-fms was more active in more differentiated normal cells and was not activated in less differentiated or dysplastic cells. c-kit, pan-ras and TP53 were not activated in normal nor dysplastic cervical cells. These results suggest EGFR, c-erbB-2 and c-myc may be important proto-oncogenes in CIN and that antibodies or anti-genes targeted against them may alter the progress of CIN to invasive cancer.
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PMID:Proto-oncogenes and p53 protein expression in normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia. 1067 85

The FHIT gene is located at a chromosomal site (3p14.2) which is commonly affected by translocations and deletions in human neoplasia. Although FHIT alterations at the DNA and RNA level are frequent in many types of tumours, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of Fhit protein expression with a large number of molecular genetic and clinical parameters in a well-characterized cohort of non-small-cell lung cancers (NSCLCs). Paraffin sections of 99 non-small-cell carcinomas were reacted with an anti-Fhit polyclonal antibody in a standard immunohistochemical reaction. Abnormal cases were characterized by complete loss of cytoplasmic Fhit staining. The Fhit staining results were then correlated with previously obtained clinical and molecular data. Fifty-two of 99 tumours lacked cytoplasmic Fhit staining, with preserved reactivity in adjacent normal cells. Lack of Fhit staining correlated with: loss of heterozygosity (LOH) at the FHIT 3p14.2 locus, but not at other loci on 3p; squamous histology; LOH at 17p13 and 5q but not with LOH at multiple other suspected tumour suppressor gene loci; and was inversely correlated with codon 12 mutations in K-ras. Fhit expression was not correlated overall with a variety of clinical parameters including survival and was not associated with abnormalities of immunohistochemical expression of p53, RB, and p16. All of these findings are consistent with loss of Fhit protein expression being as frequent an abnormality in lung cancer pathogenesis as are p53 and p16 protein abnormalities and that such loss occurs independently of the commitment to the metastatic state and of most other molecular abnormalities.
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PMID:Loss of Fhit expression in non-small-cell lung cancer: correlation with molecular genetic abnormalities and clinicopathological features. 1073 5

The aim was to investigate the combined immunoexpression of p53, p21, bcl-2, bax, Rb and Ki67 proteins in Hodgkin's lymphomas (HL) and correlate expression patterns with the histotype and the Epstein-Barr Virus (EBV) status. Paraffin-sections from 56 cases of HL (18 nodular sclerosis and 38 mixed cellularity) and from ten "reactive" lymph nodes were investigated. P53, p21, bcl-2, bax, Rb and Ki67 proteins were detected in Hodgkin and Reed-Sternberg (HRS) cells in 35/56, 56/56, 24/56, 23/56, 56/56 and 56/56 cases of HL, respectively. No correlation was found between the expression of each protein and the EBV status or the histotype of HL. Comparison between p53 and p21 staining revealed two patterns: a) p53+/p21+ (35 cases); and b) p53-/p21+ (21 cases). The pattern p53+/p21+ suggests wild type p53 protein able to induce the expression of p21 while the p53-/p21+ pattern suggests p53-independent p21 expression. These results are consistent with the interpretation that inactivating p53 gene mutations may be rare in HL. Comparison between bcl-2 and bax staining showed a statistically significant relationship (p<0.001) for coexpression (19 cases) or absence of expression of both proteins (28 cases) in HRS cells. In contrast, bax expression was observed in most lymphoid cells in all "reactive" lymph nodes. Since the proapoptotic bax protein may act as tumour suppressor it is possible that the absence of this protein in HRS cells in a substantial proportion of HL may confer growth advantage and play a role in their pathogenesis. This could suggest bax gene alterations in some HL since in other studies acute lymphoblastic leukaemia cell lines demonstrate bax gene mutations with loss of bax immunoexpression. Another possibility is that reduced bax expression may be due to post transcriptional regulation, as was described in lymphoma cell lines. Comparison between Rb and Ki67 staining disclosed two main deviations from the normal parallel relationship in reactive lymph nodes: a) 2 cases with low Rb and high Ki67 expression possibly reflecting loss of Rb expression due to chromosome loss or to other abnormalities in the structure or the expression of Rb gene; and b) 9 cases with high RB and low Ki67 possible reflecting an attempt of Rb protein in excess to induce cell cycle arrest. Taken together, our findings provide combined immunohistological evidence for deregulated expression of cell-cycle and apoptosis-related proteins, that may play a role in the pathogenesis of HL.
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PMID:Expression of p53, p21/waf1, bcl-2, bax, Rb and Ki67 proteins in Hodgkin's lymphomas. 1080 63

The object of the present study is to detect the p53 tumour suppressor gene and proliferation cell nuclear antigen (PCNA) expression in breast carcinoma by immunohistochemistry and correlate them with the prognostic parameters. Total 35 cases of primary breast carcinoma were studied and classified histologically. Paraffin sections were stained by using monoclonal antibody D07 for p53 protein and PC-10 for PCNA. Out of 35 cases, 16 (45.7%) were p53 positive and 25 (71.4%) were PCNA positive. The mean PCNA labelling index (PCNA LI +/- SD) was 58.97 +/- 22.72 in tumors positive for both p53+ and PCNA+ while cases negative for p53- and positive for PCNA+ has higher PCNA LI +/- SD (59.24 +/- 18.97). The difference in the two groups was not significant. Most cases were positive for both p53+ and PCNA+ in the age group < 30 with higher mean PCNA LI +/- SD (62.20 +/- 27.13) than in the group > 30 (57.88 +/- 18.47). In the pre-menopausal group 57.1% cases were positive for p53+ with higher PCNA LI +/- SD (59.94 +/- 24.22). Maximum p53 and PCNA positivity was observed in grade III tumors (63.2% and 84.2%). The mean PCNA LI +/- SD was also highest in grade III carcinomas (66.83 +/- 13.97). No significant correlation was found between p53 and PCNA status with morphological type and tumour size except that logistic regression showed a positive correlation with tumour grade. Therefore the present study suggests that both p53 expression and PCNA are markers of poor differentiation in breast cancer.
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PMID:Immunohistochemical localization and correlation of p53 and PCNA expression in breast carcinoma. 1092 63

Tumour growth and its progression to a metastatic phenotype involves a serious of genetic events with abnormal activation of oncogenes or inactivation of tumour suppressor genes and others genes connected with proliferation, apoptosis and neovascularisation. The aims of the study were to determine the possible prognostic value of angiogenesis, proliferation index Ki67, p53 and bcl-2 proteins expression in patients with laryngeal cancer. The group of 151 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. Paraffin--embedded tissue sections from each case were stained with a monoclonal antibody raised against FVIII antigen, p53 and bcl-2 proteins and Ki67 proliferation antigen using a peroxidase labelled streptavidin--biotin kit in standard immunohistochemistry techniques. In univariate analysis: staging IV, tumour size T4, nodal metastasis N2 and N3, local and nodal recurrences, high expression of Ki67 and P53, high (over median) IA measured as number of microvessels with FVIII expression were significantly associated with shortened overall survival. Disease-free survival was related to: proliferation index Ki67, expression of P53 protein and angiogenesis measured as microvessels density with expression of FVIII antigen. In multivariate analysis the most important death risk factors for overall survival were: tumour size, nodal metastasis, local and nodal recurrences, P53 protein expression and IA measured as number of microvessels with FVIII expression. In multivariate analysis of disease-free survival only P53 protein expression, proliferative index Ki67 and expression of FVIII had independent prognostic value. Intensity of angiogenesis, proliferation index of Ki67 antigen and expression of P53 protein were independent predictors of patients with laryngeal cancer outcome. In contrary Bcl2 protein seems to be useless in these patients.
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PMID:[Survival of patients with laryngeal cancer and some prognostic factors]. 1452 74

Archival formalin-fixed tissues from wild-caught adult blue sharks, Prionace glauca (L.), were used for immunocytochemical detection of proliferating cell nuclear antigen (PCNA), two oncoproteins from the oncogenes c-myc and pan-ras, and a protein product from the tumour suppressor gene p-53. All sharks were caught during summer months between 2000 and 2006 by recreational fishermen off the USA coast in the northwestern Atlantic. The sharks were necropsied on landing and selected organ samples were collected into elasmobranch formalin and processed for paraffin embedding and light microscopy. Paraffin-embedded sections from collected tissue were both stained with haematoxylin and eosin and processed by immunocytochemical techniques using antibodies raised against the PCNA, p-ras, c-myc and p-53 proteins. The lesions examined in this study included two well differentiated adenomatous gastric polyps, a testicular capsular mesothelioma, a gingival fibropapilloma with elements of ameloblastoma, three liver tumours, two pericardial fibropapillomas and six cases of proliferative serositis (pericarditis and peritonitis). Normal and hyperplastic tissues from blue sharks, and human neoplastic tissues served as negative and positive controls, respectively. We detected upregulation of PCNA in many neoplastic, one dysplastic and in some hyperplastic lesions, and positive p-ras and c-myc signals in some of the neoplastic lesions. None of the examined tissues showed positive p-53 signalling. This is the first literature report on immunocytochemical detection of molecular markers of cancer in sharks and in fish of the class Chondrichthyes.
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PMID:Molecular markers of cancer in cartilaginous fish: immunocytochemical study of PCNA, p-53, myc and ras expression in neoplastic and hyperplastic tissues from free ranging blue sharks, Prionace glauca (L.). 1823 18