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)

Mutation of the p53 gene which is located on chromosome 17p is the single most frequent alteration observed in human cancer. In this study we evaluate malignant melanoma, the most common intraocular neoplasm in adults, for aberrant p53 expression. Twenty enucleation specimens representing one ciliary body and 17 choroidal melanomas and two choroidal nevi were studied by immunohistochemistry utilizing the D07 anti-p53 antibody and the MIB-1 monoclonal antibody. The tumors included two spindle cell and 16 mixed cell (spindle + epithelioid cell) melanomas and two spindle cell nevi. The MIB-1 labelling index ranged from < 1% (two cases), 1-5% (13 cases) and > 5% (five cases). Of the 18 melanomas, 13 cases showed nuclear p53 staining with the p53 index < 1% (two cases), 1-3% (eight cases) and 4-5% (three cases). No p53 staining was observed in two malignant melanomas of the spindle cell type and in two choroidal nevi. In the 13 malignant melanomas of the mixed cell type, there was no correlation between MIB-1 index and p53 immunoreactivity. Immunopositivity was not found in normal choroidal melanocytes. Our study suggests that p53 alterations may be found in uveal melanomas; in our series, p53 positivity was present only in malignant melanomas of the mixed cell type.
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PMID:p53 expression in uveal malignant melanomas. 900 46

The presence of gemistocytes in low-grade astrocytomas is regarded as a sign of poor prognosis because the majority of gemistocytic astrocytomas rapidly progress to anaplastic astrocytoma or glioblastoma. To elucidate the role of gemistocytes in astrocytoma progression, we assessed the fraction of neoplastic gemistocytes, bcl-2 expression, p53 mutations, p53 immunoreactivity (PAb 1801), and proliferative activity (MIB-1) in 40 low-grade astrocytomas (World Health Organization (WHO) Grade II) with histologically proven progression to anaplastic astrocytoma (WHC Grade III) or glioblastoma (WHO Grade IV). Astrocytoma progression took significantly less time in patients with a low-grade astrocytoma containing more than 5% gemistocytes (35 months) than in those with lesions containing less than 5% gemistocytes (64 months; p = 0.038). All 11 astrocytomas with more than 5% gemistocytes contained a p53 mutation, whereas the incidence of p53 mutations in astrocytomas with less than 5% gemistocytes was 61% (p = 0.017). In low-grade astrocytomas the p53 labeling index (LI) of gemistocytes (7.4%) was significantly higher than in all tumor cells (3.2%, p = 0.0014). Gemistocytes showed a significantly higher bcl-2 expression than all tumor cells, with a mean bcl-2 1 of 15.6% versus 2.7% in low-grade astrocytomas (p = 0.0004), 20.9% versus 3.0% in anaplastic astrocytoma (p = 0.002), and 30.2% versus 5.2% in glioblastomas (p = 0.0002). In contrast, gemistocytes showed a significantly lower proliferating activity than the mean of all tumor cells, with a mean MIB-1 LI of 0.5% versus 2.6% in low-grade astrocytomas, 1.5% versus 11.6% in anaplastic astrocytoma, and 1.7% versus 16.6% in glioblastomas (p < 0.0001). These data show that low-grade astrocytomas with a significant fraction of gemistocytes progress more rapidly and typically carry a p53 mutation. The vast majority of gemistocytes are, however, in a nonproliferative state (G0 phase of the cell cycle), which suggests terminal differentiation. Their accumulation within astrocytomas may be due to bcl-2-mediated escape from apoptosis.
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PMID:Role of gemistocytes in astrocytoma progression. 904 64

The aim of this study was to determine the apoptotic cell death in 92 thyroid carcinomas of different histotypes (42 papillary, PTC; 12 poorly differentiated, PDC: 21 undifferentiated, UC; and 17 medullary, MC) by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Apoptotic index (Al, evaluated as a percentage of TUNEL-positive cells of neoplastic cells) was calculated in each tumour. The AI was very low in all subtypes of thyroid carcinoma, ranging from a median value of 0.2 in PTC to 1.4 in UC. The proliferative activity was determined by immunohistochemistry using monoclonal antibody, MIB-1. The percentage of proliferating cells was significantly different among the histotypes, increasing with tumour aggressiveness (from the mean value of 3.1 for PTC to 5.6 for PDC and 51.8 for UC). In addition, the ratio between proliferative activity and apoptosis was significantly higher in UC than in the other histotypes. The expression of bcl-2 and p53 protein (important in the modulation of cell death) was correlated (bcl-2, inverse correlation, r2 = 0.1, P = 0.04; p53, direct correlation, r2 = 0.11, P = 0.02) with apoptotic index in PTC.
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PMID:Apoptosis and proliferation in thyroid carcinoma: correlation with bcl-2 and p53 protein expression. 905 6

Cytoplasmic carcinoembryonic antigen (CEA) positivity assists in the distinction of benign and malignant glandular lesions of the cervix, but some cases remain problematic. The accumulation of p53 protein and an increased proliferative index, as measured by the expression of Ki-67 antigen, have not been used as adjuncts to the diagnosis of these lesions. Immunohistochemical stains for CEA, p53 protein, and Ki-67 antigen were performed on 31 formalin-fixed, paraffin-embedded endocervical lesions including invasive adenocarcinoma, adenocarcinoma in situ, adenoma malignum, tunnel clusters, florid microglandular hyperplasia, mesonephric remnants, florid glandular hyperplasia, atypical glandular hyperplasia, and normal controls. Ki-67 antigen expression was quantitated as negligible, low, moderate, or high on the basis of the percentage (< 5%, 5-10%, 11-40%, > 40%, respectively) of glandular nuclei that were positive with MIB-1 antibody. Strong staining of more than 10% of the glandular epithelial nuclei was interpreted as positive for p53 protein overexpression. CEA positivity was determined by either diffuse or focal cytoplasmic staining of columnar epithelial cells equalling glycocalyceal staining in intensity. The combination of CEA positivity and a moderate-to-high proliferative index was limited to cases of invasive adenocarcinoma, adenoma malignum, and adenocarcinoma in situ, as compared with benign glandular lesions (P = 0.005). A high Ki-67 proliferative index and/or CEA positivity were features of malignant lesions rather than benign mimickers; there were no false positives or false negatives. Similarly, only malignant neoplasms shared a combination of p53 overexpression and CEA positivity (P = 0.043). The combination of cytoplasmic CEA positivity in glandular cells and a moderate-to-high Ki-67 proliferative index is diagnostic of malignancy in endocervical lesions. With the exception of florid microglandular hyperplasia, p53 expression is only seen in neoplastic lesions of the endocervix. An immunohistochemical battery consisting of MIB-1 (Ki-67), p53 protein, and CEA is useful in discriminating between benign and malignant endocervical lesions.
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PMID:Immunohistochemical staining for Ki-67 antigen, carcinoembryonic antigen, and p53 in the differential diagnosis of glandular lesions of the cervix. 907 23

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.
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PMID:Biological malignancy grading in early-stage ovarian carcinoma. 907 54

Immunoreactivity of bcl-2, p53, the epidermal growth factor (EGFr) and Ki-67 (MIB-1) proteins was assessed by immunohistochemistry in 185 patients with superficial bladder cancer (SBC) in order to evaluate their usefulness as indicators of tumor progression. Forty-one percent of the tumors were bcl-2 positive, 36% of them were positive for p53 (over 20% of nuclei), while 41% were positive for EGFr, and 30% of the tumors were MIB-1 positive (proliferation index > 15%). Immunoreactivity of all analyzed proteins was highly significantly related to tumor grade and stage. Tumors which were bcl-2, p53 or EGFr positive were also rapidly proliferative (MIB-1 score >15%). The obtained results suggest that all analyzed proteins may have prognostic significance in SBC. The prognostic value of the abnormal immunolabeling of the analyzed proteins will be established after an adequate follow-up period of this same cohort of patients.
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PMID:Immunoreactivity of bcl-2, p53 and EGFr is associated with tumor stage, grade and cell proliferation in superficial bladder cancer. Finnbladder III Group. 907 39

The clinical course of renal cell carcinoma (RCC) is highly variable. Overexpression of the p53 protein has been suggested as a possible prognostic parameter in RCC. Overexpression of the mdm-2 oncogene product has been shown to interact with the p53 function. To investigate the immunohistochemical overexpression of mdm-2 protein in comparison with that of p53 protein in RCC, 50 nonpapillary pT3 RCCs were immunostained for p53 protein (DO-7) and mdm-2 (IF2). Tumor growth fraction (Ki-67 labeling index; MIB-1) was determined by immunohistochemistry. p53 positivity was detected in 16% of tumors. mdm-2 overexpression was seen in 30% of RCCs. There was a significant association between p53 and mdm-2 immunostaining (P = 0.0006), suggesting that mdm-2 protein may contribute to p53 protein stabilization in RCC. p53 overexpression was associated with a high Ki-67 LI (P = 0.0002), suggesting that p53 overexpression is involved in growth control in RCC. Survival analysis showed that Ki-67 LI (P = 0.04) and p53 overexpression were associated with poor prognosis (P = 0.0021), whereas mdm-2 overexpression was not related to patient outcome (P = 0.73). A Cox regression analysis revealed tumor stage (P < 0.001) and p53 overexpression (P < 0.05) to be independent prognostic parameters. It is concluded that p53 but not mdm-2 may be of practical relevance in predicting patient prognosis in RCC.
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PMID:p53 protein expression but not mdm-2 protein expression is associated with rapid tumor cell proliferation and prognosis in renal cell carcinoma. 907 53

Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospective series of 202 patients with stage T1a,b invasive breast carcinomas was evaluated. The clinicopathological features (age, histological grade, extensive in situ carcinoma, hormone receptor status, and nodal metastasis) as well as microvessel density and the expression of c-erb-B2, p53, MIB-1/Ki-67, and cdc25B were assessed. In addition, expression of the cell cycle inhibitor p27 was evaluated. Nineteen patients (18% of patients who had axillary dissection) had locoregional lymph node metastases. Forty-two % of them died of disease (median survival, 112 months), whereas mortality was 11% in node-negative patients (median survival, 168 months; P = 0.0055). Patients with low p27 expression had a median survival of 139 months (17% mortality) versus 174 months (9% mortality) in the group with high p27 expression (P = 0.0233). Lack of p27 was associated with poor prognosis when node-positive patients were excluded (P = 0.0252). Nodal status and low p27 were found to be the only independent prognostic parameters by both univariate and multivariate analysis, with relative risks of dying of disease of 4.9 (P = 0.001) and 3.4 (P = 0.0306), respectively. Assessment of p27, which yields prognostic information in node-negative patients, could be useful to identify patients with small, invasive breast carcinomas who might benefit from adjuvant therapy.
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PMID:The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. 910 10

Few studies have examined cell proliferation or p53 immunoreactivity in myxopapillary ependymomas. This study retrospectively examines tumor MIB-1 and p53 immunohistochemical features in 14 patients (eight women, six men; age range, 12-69 yr; median, 32 yr) with myxopapillary ependymoma. Their preoperative symptoms lasted from 2 months to 18 years (median, 12 mo) and most commonly involved lower back pain. The tumor was in the lumbar spinal cord region in 12 patients, the sacral cord in 1, and both the lower thoracic and upper lumbar cord in 1. In three patients, cerebrospinal fluid protein levels were markedly elevated, with negative cytologic results. Thirteen patients underwent a gross total resection. All of the tumors demonstrated histologic features diagnostic of myxopapillary ependymoma. Four cases had focal, prominent, nuclear pleomorphism. From 1 to 5 mitotic figures per 10 high power fields were identified in four tumors. There was no vascular proliferation or necrosis. Nine patients are alive at last known follow-up with no evidence of tumor (median, 36 mo); four are alive with residual tumor (median, 40 mo); and one died after 74 months (tumor status unknown). Eleven patients received adjuvant radiation and/or chemotherapy. Six experienced at least one tumor recurrence at intervals of 20 to 132 months. MIB-1 indices on the initial tumor resection ranged from 0 to 5.5 (median, 0.9) in 12 cases. In three patients with recurrent tumor, MIB-1 indices were higher in the initial tumor in two cases and lower in one. p53 Immunostaining of 13 tumors showed rare positive-staining tumor cell nuclei. The conclusions are that myxopapillary ependymomas grow slowly; that MIB-1 labeling indices are unreliable predictors of tumor recurrence; and that the lack of p53 immunostaining in most myxopapillary ependymomas in this series suggests that this gene might not play a significant role in the pathogenesis of these tumors.
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PMID:Myxopapillary ependymomas: a clinicopathologic study of 14 cases including MIB-1 and p53 immunoreactivity. 911 Feb 91

The proliferative activity of 30 cases of non-treated invasive ductal breast carcinoma was evaluated by bromodeoxyuridine (BrdU), proliferation marker (MIB-1) and proliferating cell nuclear antigen (PCNA), and the relation between these proliferation markers and histological subtype and histological grade were investigated. In addition, the association of these proliferation markers with overexpression of p53 protein, c-erbB-2 oncoprotein, estrogen receptor (ER) status and clinicopathologic findings were also examined. The BrdU labeling index (LI), MIB-1 score and PCNA labeling rate (LR) correlated with the histological grade. However, there was no statistical difference in proliferative activity among the histological subtypes. A linear strong correlation was demonstrated between BrdU LI and MIB-1 score (r = 0.732). Significant correlation was also found between BrdU LI and PCNA LR (r = 0.446); however, the relation between MIB-1 score and PCNA LR was weak. BrdU LI and MIB-1 score correlated positively with tumor size, TNM stage and overexpression of p53, and negatively with the presence of ER. PCNA LR correlated only with p53. These results indicate that MIB-1 is closely associated with BrdU in clinicopathologic findings and is a more useful tool for evaluating cell proliferation than PCNA. However, it will be necessary to consider the clinical significance of MIB-1 immunohistochemistry cautiously until further widespread clinical and pathological studies are performed.
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PMID:Proliferation marker MIB-1 correlates well with proliferative activity evaluated by BrdU in breast cancer: an immunohistochemical study including correlation with PCNA, p53, c-erbB-2 and estrogen receptor status. 911 Mar 47


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