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)

Thirty-seven nasopharyngeal carcinomas were studied obtaining the tissue from nasopharyngeal biopsies that were formalin fixed and paraffin embedded. The patients were born in Argentina, 23 men and 14 women with a mean age of 50 years. Histologically the tumors were classified as queratinizing squamous cell carcinomas, 1 case (2%); non-queratinizing squamous cell carcinomas, 15 cases (41%) and undifferentiated carcinomas, 21 cases (57%). The proliferating index (PI) was determined using monoclonal antibodies against PCNA and Ki-67 (MIB-1), resulting in 26% for PCNA and 17% for Ki-67 while no differences were found comparing PI with histological type and cases with clinical stage III and IV. The PI was of 2% in the 3 cases with clinical stage II. Immunostains for p53 were positive in 30 out of the 37 cases with no differences between the histological types, exception made for the queratinizing carcinoma which was negative. With a cut off point of 7% in the 12 cases with follow up, two groups were found with a mean survival of 35 and 12 months, a finding that was not statistically significant. Epstein-Barr virus was detected by PCR using the paraffin embedded material in 31 out of the 37 cases: 21 were undifferentiated carcinomas and 15 non-queratinizing squamous cell carcinomas; the queratinizing squamous cell carcinoma was negative. These results, published for the first time in samples from Argentinian patients are similar to those found in areas of high and low incidence of nasopharyngeal carcinomas and can be of clinical use in determining the nasopharyngeal origin of a cervical metastatic lymph node of an unknown primary.
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PMID:[Identification of Epstein-Barr virus in nasopharyngeal carcinomas in Argentina. Its relation with p53 and the determination of proliferation indices]. 953 23

Tissue from primary tumors was analyzed for 118 patients with urothelial cancer who subsequently received cisplatin-based chemotherapy. Immunohistochemical staining was performed for nuclear p53 reactivity; for two proposed mediators of drug resistance, metallothionein (MT) and P-glycoprotein; and for the cell proliferation marker MIB-1. For each marker, immunoreactivity was expressed as a percentage of positively staining cells, and overall intensity of staining was graded on a scale from 0 to 3. The product of these two measurements was calculated to generate a percentage-intensity index. Clinical data were obtained independently via retrospective chart review. Chemotherapy regimens containing cisplatin (cisplatin, methotrexate, and vinblastine or methotrexate, vinblastine, doxorubicin, and cisplatin) were administered for metastatic disease (n = 64), for locally advanced disease (n = 45), or as an adjuvant treatment (n = 9). The overall response rate was 56% among 99 evaluable patients, and median survival was 12.7 months. By univariate analysis, Eastern Cooperative Oncology Group performance status (P = 0.0025), tumor grade (P = 0.03), percentage of MT staining (P = 0.01), and percentage-intensity index of MT staining (P = 0.04) were significant predictors of response to chemotherapy. The first three of these were significant in a multivariate model (P = 0.05, 0.04, and 0.04, respectively). By subgroup analysis, the percentage of MT staining predicted for response in metastatic disease (P = 0.03), but not in locally advanced disease (P = 0.28). Only performance status was significantly related to overall survival (P = 0.0001, log-rank test) in the whole cohort. Overexpression of MT in the 64 patients with metastatic disease was associated with a shorter survival (P = 0.04). Expression of p53, P-glycoprotein, and MIB-1 did not predict for survival. In conclusion, overexpression of MT is associated with a poorer outcome from chemotherapy, possibly due to cisplatin resistance.
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PMID:The prognostic role of p53, metallothionein, P-glycoprotein, and MIB-1 in muscle-invasive urothelial transitional cell carcinoma. 953 22

Association of p53 gene abnormalities with tumor progression and prognosis of many neoplasms has been demonstrated, but little is known about the clinical significance of p53 abnormalities in meningiomas. The significance of p53 protein expression in recurrent meningiomas and its relationships with MDM2 protein and proliferation activity were investigated by analyzing 39 meningiomas immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was observed in recurrent meningiomas, which tended to have a high p53 positive index (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by the polymerase chain reaction-single strand conformation polymorphism method to detect p53 gene mutations, but none were found in exons 4-8 of this gene. Fifteen (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53 protein, showing that MDM2 expression was more common in meningiomas with p53 expression. p53 immunoreactivity in the absence of mutation may indicate stabilization of the wild type through interaction with the MDM2 protein. The Ki-67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53-positive tumors had a significantly higher mean MIB-1 PI than p53-negative tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be involved in controlling the proliferative activity in meningiomas. In conclusion, immunohistochemical examination for p53 protein as well as proliferative activity may help predict the malignant potential of tumor recurrence.
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PMID:Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas. 954 56

Because bronchioloalveolar carcinoma (BAC) commonly displays bland cytologic appearance, there is a good potential for misinterpretation. The aim of this study was twofold: one was to identify the most reproducible cytomorphologic features to distinguish BAC from conventional lung adenocarcinoma (CLA) on fine-needle aspiration (FNA), and the other was to investigate the staining characteristics of these two variants of lung carcinoma with P53 tumor suppressor gene immunostain and their potential value in the distinction between the two entities. Cytology records of 13 histologically documented BACs was retrieved: 7 FNA, 3 bronchial washing/bronchial brushing (BW/ BB), and 3 scraping smears of surgical specimens. Two cases had both FNA and BW/BB material. Immunostains for P53 protein, carcinoembryonic antigen (CEA), and Ki67(MIB-1) monoclonal antibodies were performed on 13 BACs (FNA cell blocks and tissue) and on 11 FNA cell blocks of CLA. Cytologically, BAC showed uniform cells with abundant, lacy cytoplasm, and bland, folded nuclei arranged singly, in papillary clusters, and sheets. Immunocytochemically, one BAC and one CLA were technically unacceptable. Of the 12 remaining BAC cases, 10 were reactive with CEA, 9 reactive with Ki67 (> 5%), and 4 reactive with P53. Of the 10 remaining CLAs, 9 were positive with CEA, 9 were reactive with Ki67 (> 5%), and 8 were reactive with P53. We conclude that BAC demonstrates distinctive cytologic features, but difficulty may be encountered with well-differentiated CLA, metastatic adenocarcinoma, and other lesions. Immunocytochemically, CEA and Ki67 do not appear to be discriminate, but P53 may be of value in distinguishing BAC from CLA. Attention to subtle nuclear changes, characteristic grouping, cellular arrangement, and P53 reactivity could enable cytopathologists to accurately diagnose BAC.
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PMID:Bronchioloalveolar carcinoma: diagnostic pitfalls and immunocytochemical contribution. 955 68

An altered control of the mechanisms involved in cell proliferation and programmed cell death (apoptosis) might play an important role in parathyroid tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell proliferation, in a series of normal and neoplastic parathyroid tissues. The specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid carcinomas. Results were scored as positive when more than 1% of cells were stained for MIB-1 and p53, and more than 10% for bcl-2. All normal parathyroids showed numerous bcl-2 positive cells (> or = 80%), low proliferation rate (MIB-1) and no p53 protein expression. Twenty-four (55%) adenomas were bcl-2 positive; in 16 of these the number of positive cells was high (> 50%) and immunoreactivity was diffusely distributed within the adenoma; 8 cases showed a zonal staining pattern, in which groups of stained cells were surrounded by negative cells. Nineteen adenomas (45%) and all carcinomas were bcl-2 negative. A high proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9%); all MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens. No significant differences in serum calcium and intact PTH levels nor in tumor size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06) correlation was observed between the percentage of bcl-2 positive cells and serum calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1 negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1 positivity). The question of whether the finding of the MIB-1 positive-bcl-2 negative phenotype identifies a subgroup of clinically more aggressive adenomas remains to be established.
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PMID:Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues. 959 Dec 7

A follow-up investigation of 25 cases of extraskeletal osteosarcomas diagnosed at the Center for Bone and Soft Tissue Tumors, Aarhus University Hospital, Denmark, in the period from 1970-1995 was undertaken. The immunohistochemical profile of these tumors was evaluated using a panel of 10 antibodies, and the value of alkaline phosphatase staining in differential diagnostic situations also was considered. The study revealed that this tumor is high-grade malignant and affects adults (median age, 67 years; range, 35-82 years) at diagnosis. The thigh (52%) was the most common tumor location. Seven tumors were superficial, whereas the remaining 18 were intramuscular. Two patients with superficial tumors previously received radiation to the area. Local recurrences developed in 9 (36%) patients and distant metastases developed in the lungs in 15 (60%) patients as the most common site. Median survival time was 24 months, and the cause-specific survival rate at 5 years was less than 25%. Thirteen (52%) intramuscularly located extraskeletal osteosarcomas were of the fibroblastic subtype, often with sparse amounts of osteoid. They could be separated from malignant fibrous histiocytoma on the basis of a strongly positive alkaline phosphatase reaction. Immunohistochemistry did not reveal characteristic features because positivity for vimentin, occasional positivity for desmin, actin, S-100, epithelial membrane antigen, cytokeratin, and p-53 may be observed in many other pleomorphic sarcomas. Various histopathologic factors, such as tumor size, tumor depth, histopathologic subtype, malignancy grade (IIIA versus IIIB), MIB-1, and p53 reactivity were analyzed in relation to clinical course. Only MIB proliferation was correlated to prognosis, with significantly longer survival in patients with tumors with MIB-1 values less than 24%. Our study has shown extraskeletal osteosarcoma to behave in a highly aggressive fashion. Alkaline phosphatase staining compared with immunohistochemistry proved to be superior in the differentiation from other pleomorphic sarcomas.
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PMID:Extraskeletal osteosarcomas: a clinicopathologic study of 25 cases. 959 29

Oncocytic neoplasms of the adrenal gland are rare. We describe the clinicopathologic and immunohistochemical findings of seven oncocytic adrenocortical neoplasms, five oncocytomas, and two oncocytic neoplasms of uncertain malignant potential. Three tumors were studied using electron microscopy. These neoplasms occurred in five women and two men (median age, 55 years) with no clinical evidence that the neoplasms were functional. The size of the neoplasms varied from 5.0 cm to 13.5 cm. Histologically, each neoplasm was composed exclusively of oncocytes. The oncocytomas had very low or absent mitotic activity and no evidence of necrosis. The two oncocytic neoplasms of uncertain malignant potential had increased mitotic activity and necrosis but no evidence of invasion or metastases. Nuclear atypia, either focal or generalized, was found in all neoplasms. Immunohistochemical studies performed using fixed, paraffin-embedded sections showed strong reactivity with the mitochondrial antibody mES-13 in all neoplasms. Four of five oncocytomas and one oncocytic neoplasm of uncertain malignant potential expressed keratin, predominantly keratin 18, as shown using the CAM 5.2 and AE3 antibodies. Two neuroendocrine-associated markers, neuron specific enolase and synaptophysin, were positive in seven and five neoplasms, respectively. However, all neoplasms were negative for the other neuroendocrine markers tested, including chromogranin A, tyrosine hydroxylase, and dopamine beta-hydroxylase, as well as for epithelial membrane antigen, S100, and p53. Using the MIB-1 (Ki-67) antibody, proliferative activity was increased in both oncocytic neoplasms of uncertain malignant potential. All six patients with available clinical follow-up data are alive without evidence disease, although the follow-up interval is relatively short (< 2 years) for the two patients with oncocytic neoplasms of uncertain malignant potential. We conclude that oncocytic adrenocortical neoplasms are nonfunctional tumors that can become large before they are detected by radiologic studies. The majority of neoplasms are benign and should not be misdiagnosed as carcinoma.
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PMID:Oncocytic adrenocortical neoplasms: a report of seven cases and review of the literature. 959 31

Esophageal cancer is very popular in Hong Kong. The tumor is often prevalent in males and has a modal peak of occurrence in the 7th decade. The pathogenesis of the esophageal neoplasm is still uncertain but likely to be multi-factorial. The commonest histological subtype is squamous cell carcinoma. Besides, mucoepidermoid carcinoma/adenosquamous carcinoma, adenocarcinoma, small cell carcinoma, sarcomatoid carcinoma, adenoid cystic carcinoma, undifferentiated carcinoma, melanoma and gastrointestinal autonomic nerve tumor are also found in a minority of patients. The proportion of various histologic subtypes is different from the Western populations. Concerning the genetic alternation, P53 mutation is common in esophageal squamous cell carcinoma. Esophageal cancer has its unique pattern of P53 mutations in Hong Kong. In addition, intramural metastasis and multiple lesions are characteristic features in esophageal squamous cell carcinoma. Important pathologic factors in determining the prognosis of patients with esophageal cancer includes completeness of surgical resection, stages, tumor dimension as well as MIB-1 scores and the presence of P53 mutations.
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PMID:Pathology of esophageal cancers: local experience and current insights. 959 48

In this study, we report our results on the proliferative activity of ependymomas as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we compare our results with those obtained by immunolabeling with monoclonal antibodies to p53 and bcl-2 proteins to assess whether expression correlated with ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II), and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001), with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic standard error = 108). In addition, one ependymoma (WHO Grade II) not considered overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling index, suggesting that the MIB-1 proliferation index might be a more objective indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas showed low proliferative activity. bcl-2 oncoprotein expression was identified in all of the four myxopapillary and in both papillary ependymomas. An additional observation was the correlation of p53 expression with increasing WHO grade. These data suggest that high MIB-1 and p53 immunolabeling might be objective indicators of high grade in ependymomas that do not otherwise meet routine histologic criteria for high-grade ependymoma. Subsequent clinicopathologic analyses will be important in assessing whether these markers are useful as independent predictors of survival.
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PMID:Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype. 961

Using immunohistochemistry we evaluated the expression of two negative regulators of the cell cycle, the retinoblastoma gene product (pRb) and the WAF1/Cip1 gene product (p21), in consecutive paraffin sections from 54 gliomas (49 astrocytomas and 5 oligodendrogliomas) and related it to clinicopathological parameters, proliferative fraction, p53 expression and survival. Survival analysis was restricted to the group of diffuse astrocytomas (48 patients). pRb expression did not correlate with histological type, grade or p53 expression, while a moderately strong correlation existed between pRb expression and the percentages of proliferating cell nuclear antigen (PCNA) and MIB-1-positive cells. In 30% of cases we observed diminished pRb expression (i.e., a low pRb/Ki-67 ratio), irrespective of grade or histological type. p21 protein was elevated in 50% of cases, especially within the higher grades. The percentage of p21-positive cells was not related to histological type or grade but correlated loosely with PCNA and pRb expression. A p53-negative/p21-negative phenotype was characteristic of oligodendrogliomas and low-grade astrocytomas, whereas the p53-positive/p21-positive, p53-positive/p21-negative and p53-negative/p21-positive phenotypes were almost equally distributed among high-grade tumors. In survival analysis (either univariate or multivariate) diminished pRb expression was not a statistically significant prognostic indicator. In contrast, p21 expression emerged as an important indicator of shortened disease-free survival, in both univariate and multivariate analyses. Moreover, the double-positive p53/p21 phenotype tended to be associated with a shorter overall survival. Our results suggest that Rb gene deregulation does not significantly affect prognosis but p21 expression may play an important role in disease-free survival of astrocytoma patients.
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PMID:Expression of retinoblastoma gene product and p21 (WAF1/Cip 1) protein in gliomas: correlations with proliferation markers, p53 expression and survival. 965 Jul 54


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