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)

A series of 222 tumor samples stored at -80 degrees C in the authors' tumor library were investigated with anti-p53 (PA 1801) and streptavidin-biotin-peroxidase complex. The p53 immunoprecipitates were quantified by densitometry assessed by image analysis of digitized microscopic images. Two parameters, percentage of positive surface and mean optical densities, were compared with the patient's outcome (follow-up = 96.8 months) (life table method, Mantel Cox test, BMDP statistical software). The p53 expression significantly correlated with a poor overall survival (P = .0063), metastasis-free survival (P = .024), and recurrence-free survival (P = .022) at a 20% cutoff point of positive immunoreactive tumor surface. A strong prognostic significance was observed in the node-positive subset of patients but not in the node-negative subset, except for recurrence-free survival (P = .047). The results indicate the clinical relevance p53 evaluated by quantitative immunocytochemistry.
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PMID:Quantitative immunocytochemical assays on frozen sections of p53: correlation to the follow-up of patients with breast carcinomas. 892 75

The expression of ras-encoded p21 and p53 proteins was analyzed by immunohistochemical staining with monoclonal antibodies in 26 paraffin-embedded specimens (25 endometrial carcinomas and 1 uterine carcinosarcoma) taken from Polish women. The biotin-streptavidin-peroxidase detection system was employed. ras p21 protein was expressed in 68% of the specimens and p53 positive staining was noted in 36% of the carcinomas. Simultaneous expression of the ras p21 and p53 proteins was demonstrated in 8 (32%) out of the 25 specimens. Except one case, where the p53 protein was expressed, ras p21 protein was also detected. Both proteins were demonstrated in the sole case of carcinosarcoma. A difference between the detection of simultaneous expression of the ras p21 and p53 proteins in correlation with FIGO stages I to II-IV has been reported (22% v. 57% respectively). These data indicate, that ras p21 correlated with p53 positive staining in one-third of the endometrial cancers analyzed. The simultaneous detection of both proteins correlated with the advanced clinical stage of human endometrial carcinomas.
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PMID:Simultaneous expression of the ras p21 and p53 proteins in human endometrial carcinomas. 896 Mar 5

In immunohistochemistry, it is well known that the majority of monoclonal antibodies to keratins work best on fresh frozen tissue specimens, yet in clinical practice most biopsies are routinely fixed in formaldehyde. This seriously limits the range of keratins that can be reliably assessed in retrospective studies (particularly where only rare archival material exists) and where subtle changes during tissue differentiation may be important. Antigen retrieval using exposure to microwave radiation is one technique that has been applied successfully to other tumour markers (e.g., p53). However, few papers have used this method when immunolabelling for keratins, in spite of the widespread use of antikeratin antibodies as markers of differentiation. The effect of keratin antigen retrieval using microwave processing was assessed on a range of oral mucosal biopsies, since the oral cavity displays a wide range of keratins. A panel of six well characterized antibodies was chosen: LP34 (Ck1, 5, 6, 18), LH1 (Ck10), LL025 (Ck16), A53 BA2 (Ck19), AE8 (Ck13), and E3 (Ck17). For each specimen, one piece was stored in liquid nitrogen and another piece fixed in formalin. Tissue sections were cut from each and, using the peroxidase avidin biotin technique, keratin expression was recorded for a frozen section, a dewaxed section, and a microwave-heated dewaxed section. Although overall there was a 25% improvement in identification of keratins after microwaving, some antibodies performed better than others. Given that keratins have been shown to be of value in tumour diagnosis, this study suggests that microwave processing of archival material can be a valuable adjunct to such analysis.
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PMID:Keratin antigen retrieval in oral mucosal biopsies using microwave processing. 901 9

Detection of p53 expression has been reported to be associated with poor prognosis in a variety of human malignancies. The aim of the current study was to utilize immunocytochemical antigen detection techniques to search for evidence of altered p53 protein overexpression in 43 primary osteosarcomas (OS). The study was carried out on formalin fixed, paraffin-wax embedded 3 to 4 microns, previously decalcified OS tissue sections. A four step biotin-streptavidin based method was employed with peroxidase conjugation as the enzymatic label. Presence of a frequent level of p53 protein expression was detected in all 43 primary osteosarcomas, suggesting a frequent p53 gene mutation. p53 protein alterations were also associated with all grades of cell microenvironment heterogeneity in the observed OSs. Overexpression of the p53 protein was detected in 31/43 (72%) primary OS cases. Formalin fixed and paraffin-wax embedded human breast carcinoma tissue sections were employed as positive control tissue. p53 protein absence was demonstrated in normal postnatal thymus, serving as the negative control tissue. Our results lead us to the following conclusions: a) the altered p53 gene product is detectable employing the chosen mouse anti-human MoAB in decalcified, formalin fixed, paraffin-wax embedded, routine tissue sections of OSs and breast carcinomas which provides an opportunity for numerous retrospective studies and comparison with additional immunodiagnostic indicators; b) primary OSs with similar cell differentiation may be genetically heterogeneous; c) p53 gene or protein alterations represent early, immunodiagnostic markers of a malignant immunophenotype (IP) in various human neoplasms, including OSs; and d) immunomorphological techniques and in situ hybridization should be employed as methods to collect data for computerized, quantitative image analysis (IA) of the cellular accumulation and localization of the altered p53 protein.
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PMID:Immunohistochemical detection of p53 protein overexpression in primary human osteosarcomas. 906 1

Loss of heterozygosity (LOH) on chromosome 17 is a frequent genetic alteration in breast cancer. To assess whether the location of potential tumor suppressor genes is compatible with the LOH pattern in individual tumors, we analyzed allele loss on chromosome 17 in 121 invasive ductal breast carcinomas and 16 benign breast tumors with 14 polymorphic microsatellite markers (4 on 17p and 10 on 17q). Fluorescent polymerase chain reaction (PCR) for typing microsatellites coupled with DNA fragment analysis in an automated DNA sequencer was applied. Frequencies of LOH varied from 29.4% (D17S1322) to 57.4% (TP53-Alu). No LOH could be detected in benign breast tumors. In 54 tumors the deletion patterns were consistent with the complete loss of 17p (n = 28), 17q (n = 9) or the whole chromosome 17 (n = 17). Five smallest regions of overlap (SROs) were identified in tumors with interstial deletion patterns. On 17p, two foci were detected affecting the TP53 locus and the hypermethylated in cancer I (HICI) region (17p13.3). On 17q, SRO1 was localized between markers THRAI and D17S855, centromeric to the breast/ovarian cancer gene BRCAI; SRO2 was flanked by markers AFM234 and NMEI, and SRO3 was centered between markers MPO and GH. Associations between LOH and histopathological characteristics were determined. Significant correlations were found between higher grade and loss of the TP53 gene (marker TP53, P = 0.019), loss of the BRCAI region (P < 0.009), LOH of marker AFM155 (P = 0.003) and marker NMEI (P = 0.026). For positive estrogen receptor status, only LOH of the THRAI marker correlated significantly, whereas highly significant correlations were determined between positive progesterone receptor and markers centromeric to the BRCAI region D17S250 (P = 0.00002), THRAI (P = 0.0006), and the intragenic BRCAI markers [D17S1322 (P = 0.021), D17S855 (P = 0.029)]. Results presented in this study identify five independent regions of chromosome 17 which are likely to contain potential tumor suppressor genes involved in the carcinogenesis of sporadic breast cancer.
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PMID:Patterns of allelic loss on chromosome 17 in sporadic breast carcinomas detected by fluorescent-labeled microsatellite analysis. 907 71

Immunohistopathological staining for p53, PCNA and Ki67 was performed in 120 specimens from previously untreated laryngeal carcinomas using the avidin-biotin method with peroxidase as a marker enzyme and diaminobenzidine as a chromogen. A 5-grade staining score system was used. Statistically significant correlations (Chi-square) were seen between T- and N-stage and histopathological grading. p53 and Ki67 scoring correlated with T- and N-stage whereas PCNA with T-stage. All staining correlated with histopathological grading. The score of staining for p53, PCNA and Ki67 correlated with each other. The patients with recurrences within 3 years had mainly carcinomas with higher staining scores. Using Chi-square analysis the p53, PCNA and Ki67 staining scores were also independent prognostic indicators.
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PMID:p53, PCNA and Ki67 in laryngeal cancer. 909 9

Accumulation of p53 protein has been considered an intermediate biomarker in multistage oesophageal carcinogenesis. The aim of the present study was to investigate p53 expression by immunohistochemistry in 13 thoroughly sampled oesophagectomy specimens from a geographical area with a high oesophageal cancer incidence (Basse Normandie, France). Expression of p53 was looked for in tissue samples of cancer, intraepithelial neoplasia, and uninvolved mucosa. The streptavidin biotin peroxidase complex method was used for p53 immunostaining. p53 expression was found in invasive squamous cell carcinoma in 8 out of 11 cases and in intraepithelial neoplasia in 10 out of 11 cases. In all 13 cases, in uninvolved oesophageal mucosa, expression of p53 was focally present in areas of chronic oesophagitis. Chronic oesophagitis has been regarded by epidemiologists as a precursor lesion for squamous cell carcinoma of the oesophagus. Since oesophageal carcinogenesis is a multistage process, the study of precursor lesions could provide information on the timing of p53 gene abnormalities during oesophageal carcinogenesis. These preliminary data require to be confirmed by molecular analysis of the p53 gene.
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PMID:Expression of p53 in oesophageal squamous epithelium from surgical specimens resected for squamous cell carcinoma of the oesophagus, with special reference to uninvolved mucosa. 977 89

Detection of p53 protein expression and overexpression has been reported to be associated with poor prognosis in a number of human malignancies. The aim of this study was to utilize immunocytochemical antigen detection techniques to search for evidence of abnormal p53 protein accumulation in ten human childhood astrocytoma (ASTR) subtypes (five pilocytic, two pure anaplastic, one anaplastic ASTR with primitive neuroectodermal tumor elements, one ASTR containing a majority of oligodendrocytes and one glioblastoma multiforme). The immunocytochemistry was carried out on routine, formalin fixed, paraffin-wax embedded 3 to 4 microns thick ASTR tissue sections. A four step, indirect, biotin-streptavidin based method was employed with peroxidase enzyme conjugation. Surprisingly, p53 protein expression was demonstrated in all ten ASTRs. The immunoreactivity pattern was mostly heterogeneous, with cells groups of similar intensity clustered within the ASTRs. The number of cells stained and the intensity of the immunoreactivity correlated directly with the known degree of malignancy of the various subtypes of ASTRs: lowest in the pilocytic ASTR cases and highest in the glioblastoma multiforme. Low-grade human ASTRs possess an intrinsic tendency for cell dedifferentiation toward the embryonic cell immunophenotype (IP). Loss of p53 function is associated with most, if not all, human malignancies. Mutation of p53 has yet to be demonstrated in pilocytic ASTRs. The accumulation of p53 in some pilocytic ASTR cells, as demonstrated in our study, suggests that the mere dysfunction of the p53 protein may be involved in the ealry stages of ASTR progression from the grade I pilocytic subtype to the more "malignant" pure ASTR, which is characterized by p53 gene mutations. The loss of p53 provides the necessary genetic instability needed for further IP changes and further progression towards more malignant IPs, e.g. anaplastic ASTR and glioblastoma multiforme. Such facts make the use of p53 in the assessment of ASTRs indispensible. p53 levels may be used in identifying cell clones within pilocytic ASTR microenvironments, which have a clear tendency for progression toward more malignant IPs and the establishment of the alteration of the p53 gene in more advanced ASTR subtypes (grades II to IV).
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PMID:Immunohistochemical detection of p53 protein expression in various childhood astrocytoma subtypes: significance in tumor progression. 913 69

Thirty-two cases of squamous cell carcinoma (SCC) of the skin were investigated as to the expression of p53 and p21 (WAF1/CIP1) using an immunohistochemical method. These cases were surgically resected or biopsied, tissue samples were then fixed in formalin and embedded in paraffin in the conventional way. Microwave heating was used for antigen retrieval. The primary monoclonal anti-p21 antibody and the monoclonal antibody against p53 were employed. The labeled-streptoavidin-biotin-peroxidase method was used for immunohistochemical staining. Of these, 30 cases showed overexpression of p53 staining, but normal epidermal cells were free of stain. p21 positive cells were detected faintly in the middle layer cells of normal epidermis. Of these, 30 cases showed overexpression of p21 staining. The staining pattern of p53 and p21 showed intratumoral heterogeneity in SCC. In general, there was the inverse relationship between p21 and p53 staining in tumors, namely p53 positive cells were p21 negative and vice versa. However, some of the tumor cells expressed both genes simultaneously. This study supports a hypothesis that p21 expression is regulated by p53, and that it is also regulated by an additional pathway(s) in SCC.
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PMID:Immunohistochemical detection of p21WAF1/CIP1 and p53 proteins in formalin-fixed paraffin-embedded tissue sections of squamous cell carcinoma of the skin. 913 81

P53 is overexpressed in more than 50% of all human cancers. A previous study suggested that p53 was also overexpressed in oral papillomas. This study was carried out to investigate whether p53 expression was correlated with expression of the cellular proliferation marker Ki-67 and the epithelial differentiation marker cytokeratin-4 (CK4) in oral papillomas. Formalin-fixed paraffin-embedded sections of 30 oral papilloma specimens and 30 unmatched normal oral mucosal specimens were processed for immunohistochemistry, using an avidin-biotin-peroxidase procedure and monoclonal antibodies. A semiquantification analysis on p53 and Ki-67 labeling indices was performed. Twenty-eight of 30 (93%) papilloma specimens were positive for p53. The percentage of p53-positive cells in the basal layer was 60.4 +/- 14.8 (mean +/- SD, n = 28), and that of Ki-67-positive cells was 26.7 +/- 14.4. There was no correlation between expression of p53 and that of Ki-67. Expression of CK4 was inversely correlated with the expression of Ki-67 but not correlated with the expression of p53.
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PMID:Expression of p53, Ki-67 and cytokeratin-4 (CK4) in oral papillomas. 917 72


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