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)

Ki-67 and P53 expression were studied using immunohistochemistry on tissue samples obtained during transurethral electroresection or needle biopsy in 62 patients with prostatic lesions: group 1 (n = 15)--benign prostatic hyperplasia (BPH), group 2 (n = 10)--high-grade prostatic intraepithelial neoplasia (PIN 3), group 3 (n = 10)--low-grade prostatic carcinoma (PC, Gleason score 2-4), group 4 (n = 12) intermediate-grade prostatic carcinoma (PC, Gleason score 5-7) and group 5 (n = 15) high-grade prostatic carcinoma (PC, Gleason score 8-10). Moreover, in the groups examined the associations between expression of Ki-67 and P53 were analysed. Paraffin-embedded tissue samples were immunostained with monoclonal antibody anti-P53 and polyclonal antibody anti-Ki-67 using avidinbiotin-peroxidase method. Our study revealed lack of Ki-67 and P53 immunoreactivity in BPH. Only 3 out of 10 high-grade PIN exhibited Ki-67 positivity, but there was no immunopositivity of P53 protein in this group. Although immunopositivity of Ki-67 increased with the histological grade of prostatic cancer, the differences in Ki-67 expression between intermediate and high-grade cancer did not reach statistical significance. A similar level of Ki-67 reactivity in intermediately-differentiated and poorly-differentiated prostate cancer suggests a similar biology of these cancers. P53 protein positivity was noted in 62.2% cases of prostate cancer. Moreover, the highest level of P53 accumulation in intermediate-grade carcinomas may predict the aggressive progression and risk of metastases in these cases. No significant differences in P53 immunopositivity between low-grade and high-grade PC were noted. Interestingly, only in low-grade PC there was a significant positive correlation between expression of Ki-67 and P53 protein.
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PMID:Ki-67 antigen and P53 protein expression in benign and malignant prostatic lesions. Immunohistochemical quantitative study. 1083 1

Biomarker data may provide a way to strengthen the link between environmental tobacco smoke (ETS) exposure and lung cancer shown in epidemiological studies. We conducted a multicenter case-control study to investigate the association between ETS exposure and lung cancer in never-smokers using p53 mutations as a biomarker of tobacco-related carcinogenesis. Paraffin-embedded tissue or fresh tissue samples from 91 never-smokers and 66 smokers with histologically confirmed lung cancer and interview data about smoking habits and ETS exposure were analyzed for mutations in the p53 gene. Statistical analysis was performed using multivariate logistic regression. Among the lifelong nonsmokers, the overall mutation prevalence was 10% (nine cases). Among 48 never-smokers ever exposed to spousal ETS, 13% (six cases) showed mutations. Smokers exhibited 17 (26%) mutations. A 3-fold [odds ratio, 2.9; 95% confidence interval (CI), 1.2-7.2] increased risk of p53 mutation was observed for smokers as compared with all never-smokers combined (i.e., irrespective of ETS exposure). The increase was 4.4-fold (95% CI, 1.2-16.2) when compared with never-smokers without ETS exposure. Among never-smokers, the risk of mutation was doubled (odds ratio, 2.0; 95% CI, 0.5-8.7) for exposure to spousal ETS only, based on 6 exposed cases with mutation and 42 exposed cases without mutation. The risk was 1.5 (95% CI, 0.2-8.8) for those ever exposed to spousal or workplace ETS as compared with those never exposed to spousal or workplace ETS. For smokers, the most common mutation type was G:C to T:A transversion (31%), whereas G:C to A:T transitions were predominant among never smokers (57%). In conclusion, our study indicates a significant 3-4-fold increased risk of p53 mutation in smoking lung cancer cases, and it suggests that mechanisms of lung carcinogenesis in ETS-exposed never-smokers include mutations in the p53 gene, similar to that seen in smokers. However, the mutation patterns observed also suggest a difference between smokers and never-smokers. Clearly, additional investigations of the role of p53 mutation as a biomarker for tobacco-related carcinogenesis, including that related to ETS, are indicated.
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PMID:p53 mutations and exposure to environmental tobacco smoke in a multicenter study on lung cancer. 1085 Apr 36

Paraffin-embedded tissue slides from 88 infiltrating ductal breast carcinoma were examined by immunohistochemistry technique with the use of monoclonal antibody against human p65 antigen and polyclonal antibody against p65-like protein present in fetal bovine serum. Immunohistochemical analysis of expression of growth factor receptors (EGFR), protein product of oncogene c-erb B2 as well as protein product of mutated anti-oncogene p53 was also done. It was established that there is no correlation between p65 and c-erbB2, EGFR or p53 expression. In low differentiated tumors (grade III) high p53 index and high EGFR and c-erbB2 expression was connected with low p65 expression. The lack of c-erbB2 and EGFR and low p53 expression was combined usually with high p65 oncoprotein levels.
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PMID:Immunohistochemical analysis of expression of a 65 kDa oncofetal protein (p65), epidermal growth factor receptor (EGFR), oncogene c-erb B2 and tumor suppressor gene p53 protein products in breast cancer patients. 1087 Jun 81

Immunohistochemistry for Topoisomerase II alpha (TopoIIa), a nuclear protein important for the separation of chromosomes and deoxyribonucleic acid replication, provides insight into the molecular events in the cell cycle and the response to chemotherapeutic agents, which target TopoIIa. We test the hypothesis that the percentage of TopoIIa immunoreactive nuclei (TopoIIaI) aids in the treatment and prognostic evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs) and correlates with established cell cycle control markers: p53, p21WAF1/CIP1 (p21), and Ki67. Paraffin sections from a retrospective surgical series of 108 SENs were immunostained with anti-TopoIIa, anti-p53, anti-p21, and anti-Ki67. The TopoIIaI, the Ki67 proliferation index (Ki67PI), and the immunoreactivity score for p53 and p21 (IMS: S1, S2, S3 < 10%, 10 to 50%, > 50% of strong staining cells, respectively) were evaluated manually. TopoIIaI and Ki67PI ranged from 5 to 84% and 4 to 88% (mean/median: 31/30 and 44/46%), respectively, and were correlated (coefficient 0.62, p < 10(-11)). IMS of 108 SENs was as follows: p53 50% + (2S1, 52S3) and p21 66% + (38S1, 12S2, 21S3). The TopoIIaI associated directly with p53 (p < 10(-5) and inversely with p21 (p < 0.005) IMS. TopoIIaI correlated with SEN architectural/nuclear grade (p < 10(-5)/10(-7)), but not histologic type. Sixty-seven patients had disease at last follow-up, 55 were dead from disease at 2 to 67 months (mean/median 24/21), and 14 were alive with disease at 31 to 230 months (mean/median 73/59). Forty-one patients were disease free at 5 to 228 months (mean/median 75/54). TopoIIaI correlated with presence of disease (p < 0.01) and poor survival (p < 1 x 10(-9), even when only 93 invasive SEN cases are considered (p < 0.005). TopoIIaI correlates with poor prognosis and other cell cycle control markers. The patients in this retrospective series of SEN were treated primarily with platinum-based chemotherapy. These data may suggest further prospective studies in which patients with SENs exhibiting high TopoIIaI are treated with chemotherapy targeted against TopoIIa (e.g., etoposide). In this retrospective series, high SEN TopoIIaI predicted poor survival when treated with platinum-based chemotherapy, which does not target TopoIIa.
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PMID:Topoisomerase II alpha: prognostic predictor and cell cycle marker in surface epithelial neoplasms of the ovary and peritoneum. 1090 74

p53 abnormalities constitute the most frequent genetic alterations identified in larynx cancers. p53 overexpression in histologically "tumor-free" surgical margins correlates with a high recurrence rate. However, only 50-60% of tumors overexpress p53. The tumor marker eIF4E is overexpressed in 100% of larynx cancers, and overexpression of eIF4E in histologically "tumor-free" margins predicts a significantly higher recurrence. We undertook this study to correlate the expression of p53 and eIF4E in the tumors and surgical margins of squamous cell cancers of the larynx and to determine their prognostic value. A retrospective analysis was performed on 54 patients who underwent surgery for squamous cell cancers of the larynx. Patient and tumor characteristics were reviewed, and the time to recurrence was noted. Paraffin-embedded sections from the tumors and surgical margins were immunostained with antibodies to eIF4E and p53, and a qualitative analysis was performed. All 54 patients (100%) overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were p53 positive. Thirty-two of the 54 patients (59%) had eIF4E-positive margins. All 6 of 53 patients (11%) with p53-positive margins also overexpressed eIF4E in the margins. There was a significant correlation between p53 and eIF4E being positive in the margins (Spearman's correlation coefficient, P = 0.03). Twenty-one of the 25 patients (84%) that recurred, including the 6 patients with p53-positive margins, had eIF4E-positive margins. Hence, although the univariate analysis showed that nodal status and both eIF4E and p53 expression in the margins were significant predictors of recurrence (P < 0.05), in the multivariate analyses only nodal status (P < 0.001) and eIF4E in the margins (P < 0.001) were significant predictors of recurrence. Kaplan-Meier analysis demonstrated that the disease-free intervals for eIF4E-positive margins were significantly shorter than eIF4E-negative margins (P = 0.0007). There was no additional effect to the combination of positive p53 and eIF4E margins (P = 0.21). The overexpression of eIF4E in the margins appears to be a more sensitive indicator of recurrence and may be an earlier event in the process of tumorigenesis than p53.
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PMID:Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications. 1091 74

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

The purpose of the present study was to estimate p53 and c-erbB2 expression in an Egyptian cohort and assess their relationships with other indicators of aggressive disease. Additionally, the frequency of both oncogenes was compared to that reported in other breast cancer populations. Paraffin-embedded tissue sections obtained from 210 invasive ductal carcinomas were evaluated immunohistochemically for p53 and c-erbB2 oncoproteins using CM-1 polyclonal antibody and mAb1 monoclonal antibody, respectively. Tumor proliferation was also assessed using PC10 anti-PCNA (proliferation cell nuclear antigen) monoclonal antibody. Chi square test was used to assess the relationship between p53 and c-erbB2 and their associations with other prognostic factors. The results revealed that p53 and c-erbB2 were equally expressed, each accounting for 40% of the total cases (84 out of 210) Immunoreaction for p53 and/or c-erbB2 was demonstrated in 65% (136 out of 210) and 15% (32 out of 210) were positive for both oncogenes. Poor histologic grade was more significantly associated with p53 expression (P = 0.0001) than c-erbB2 expression (P = 0.01). The latter was also significantly associated with premenopausal status (P = 0.01) and large tumor size (P = 0.003). Both p53 and c-erbB2 oncoproteins were found to be unrelated to each other, nodal status or PCNA immunostaining. These data suggest that p53 and c-erbB2 oncogenes correlate with poor prognostic features of breast cancer. The differences between the frequency of p53 and c-erbB2 expression observed in this study and in the reports of Western authors will hopefully stimulate investigation of these oncogenes using molecular biologic techniques and matched comparative Egyptian and European breast cancer groups.
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PMID:Immunohistochemical expression of p53 and c-erbB2 proteins in breast cancer in Egypt. 1092 68

Although ras oncogenes and p53 tumor suppressor gene mutations are implicated in the development of several human tumors, little is known about their role in the pathogenesis of primary cardiac tumors. Paraffin-embedded tissue from 19 cardiac myxomas were investigated for the presence of ras oncogenes and p53 tumor suppressor gene abnormalities. Immunohistochemical analysis was used to identify the accumulation of p21-ras and p53 proteins. A polymerase chain reaction was used to amplify exons 1 and 2 of the ras genes and exons 5 to 8 of the p53 gene. The PCR products were analyzed by single strand conformation polymorphism analysis and by direct DNA sequencing. Three of 19 myxomas showed strong positive staining for the ras p21 protein. In contrast, nuclear p53 was not detectable in any of the myxomas. Among the ras p21 immunopositive myxomas, 2 were heterozygous for a missense point mutation of the K-ras, Gly 12Asp. Further screening of the remaining myxomas showed no mutation or even silent polymorphism in any exon of the ras and p53. The results suggest that although genetic alterations of ras oncogenes and p53 are uncommon events in cardiac myxomas, ras mutations may be involved in the pathogenesis of a subgroup of this type of tumor.
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PMID:Ras oncogenes and p53 tumor suppressor gene analysis in cardiac myxomas. 1099 33

To analyze relevant factors and their effects on neoplastic progression in cervical carcinoma, a panel of genetic markers was studied. Paraffin-embedded tissue sections were obtained from 37 patients with carcinoma of the uterine cervix, 14 noninvasive squamous cell carcinomas (NISCCs), and 23 invasive squamous cell carcinomas (ISCCs). Immunoreactivity of Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. Positive staining of Msh2 was detected in 13 of 14 (92.9%) NISCCs and in 13 of 23 (56.5%) ISCCs (P < 0.02). Mlh1 immunoreactivity was observed in 10 of 14 (71.4%) NISCCs and in 8 of 23 (34.8%) ISCCs (P < 0.04). Overexpression of p53 protein was found in 4 of 14 (28.6%) NISCCs and in 16 of 23 (69.6%) ISCCs (P < 0.02). Bcl-2 overexpression was detected in 2 of 14 (14.3%) NISCCs and in 15 of 23 (65.2%) ISCCs (P < 0.003). No significant difference in the two types of lesion was found for Bax and Fhit expression. The relationship between Mlh1, Msh2, and p53 protein expression was significant (P < 0.001 and P < 0.001, respectively), as was that between Fhit and Bax immunoreactivity (P < 0.02). In conclusion, we consider that altered expression of Msh2, Mlh1, p53, and Bcl-2 may be a critical event during cervical cancer progression, whereas Fhit may be a component of a proapoptotic pathway.
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PMID:Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix. 1099 51

In a previous study, we demonstrated that the G1 cell cycle checkpoint in carcinomas of the breast is frequently abrogated by loss of p16, the product of the CDKN2/INK4A gene, and, to a lesser extent, by loss of pRB, the product of the retinoblastoma gene. The purpose of the present study was to determine whether other mechanisms of cell cycle deregulation exist in breast cancers which have retained RB and p16 function. Paraffin sections of 81 invasive breast carcinomas (49 ductal, 26 lobular, 6 mixed) were reacted with monoclonal antibodies against cyclin D1 and p53, using optimized immunohistochemical staining protocols. The staining results were correlated with the expression of p16 and pRB, and with a variety of pathological parameters and DNA ploidy. Twenty-five tumors (31%) accumulated (presumably mutant) p53 and 28 (35%) overexpressed cyclin D1; 7 carcinomas (not including any pure lobular cancers) abnormally expressed both proteins. p53 accumulation correlated with nuclear, mitotic, and overall grade, but not with tumor size, lymph node involvement, or DNA ploidy. Overexpression of cyclin D1 was not associated with any of the patho-biological variables. There was an inverse correlation between loss of p16 and high levels of p53, but not cyclin D1. The G1 cell cycle checkpoint, which is controlled by RB, cyclin D1, and p16, was abrogated in 65% of carcinomas, and only p53 was abnormal in an additional 17%. The number of abnormally expressed genes correlated with mitotic activity and overall tumor grade, but not with tumor histology, size, or nodal status, suggesting that cell cycle deregulation is an early event in breast tumorigenesis. Only 18% of the carcinomas showed a normal level of expression of the four genes tested, and p16 appeared to be the most common target of cell cycle deregulation. These data point to the importance of cell cycle regulatory protein abnormalities in human breast cancer.
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PMID:Abnormal expression of cell cycle regulatory proteins in ductal and lobular carcinomas of the breast. 1100 34


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