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)

The first cyclin dependent kinase inhibitor to be discovered was the p21 cdk interacting protein (a.k.a., WAF1, Cip1, CAP20, Sdi1, mda6). p21 expression may or may not be dependent on p53. This pathway also inhibits DNA replication by merit of p21's interaction with PCNA, but it has also been shown that this same inhibitory interaction with p21 does not affect PCNA DNA repair abilities. We assessed the immunohistochemical expression of p21 protein in 60 curative surgical resected non small cell lung cancers relating it to the expression of PCNA to clarify the contribution of the p21/PCNA pathway to the development of NSCLC. We did not find any relationship between PCNA and p21 expression. This last result may indicate that the mechanism by which PCNA controls the DNA repair is the most important activity of this protein during lung cancer progression and development, compared to its contribution to cell proliferation. In fact, this last event is strongly counteracted by p21 expression, which in this last case works as an inhibitor of PCNA expression. In conclusion this study highlighted the important role of the p21/PCNA pathway in lung carcinogenesis, pointing out the contribution of PCNA to the response to lung aggression and not only it's role as a proliferation index. Therefore, these results offer a background to further study to evaluate potential novel therapeutic approaches to lung cancer treatment.
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PMID:Expression of p21 in non small cell lung cancer relationship with PCNA. 1106 57

160 clinically non-secreting pituitary adenomas were examined in regard to their expression of the markers PCNA, bcl2, Ki 67 in the mib-1 modification and p53 which are still under investigation for their relevance to cell proliferation. The series contained 60 null cell adenomas, 60 oncocytomas and 40 gonadotroph adenomas. The groups that showed a definitely negative and definitely positive staining were evaluated in regard to their further characteristics such as size, invasiveness and recurrence. PCNA showed a highly represented immunostaining index throughout the groups, but not correlation between the PCNA index and an increased recurrence rate could be found. The staining for bcl2 was only rarely positive and only in a small number of cells. No correlation with the clinical data could be seen. We found a significant higher rate of staining in the invasive adenomas in the group of null cell adenomas and oncocytomas for Ki 67, especially in those adenomas expressing p53. p53 positivity was restricted to the invasive adenomas but was found only in 20% of all invasive adenomas. These data confirm in a sufficiently large series of clinically endocrine inactive pituitary adenomas, that p53 and Ki67 immunohistology is useful in evaluating the aggressive behavior of clinically silent pituitary adenomas. Nevertheless, negative results do not exclude clinically relevant invasive behavior.
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PMID:Proliferation markers in different types of clinically non-secreting pituitary adenomas. 1108 Dec

Paragangliomas of the nasal cavity and paranasal sinuses are extremely rare. This study was conducted to investigate the biologic characteristics of these lesions on different molecular levels and to estimate their biologic behavior. Operative specimens of three patients who underwent surgery for a paraganglioma of the nasal cavity (one case) or paranasal sinuses (two cases) were investigated by routine histology, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e., Proliferating Cell Nuclear Antigen, PCNA; Ki67-MIB-1), the expression of cell-surface antigens, which reflect the tumor-stroma interaction (i.e., CD 44 v0.4/5 and 6, CD 54, CD 106), oncogene products (nm-23; p53), and bcl-2 as a marker of apoptosis. Histologically, two tumors were paragangliomas of the adenomatous subtype, one lesion was classified as angiomatous. According to DNA analysis, aneuploid cells were detected in all tumors. Two of three paragangliomas were classified as a DNA type III pattern, implying a high percentage of aneuploid cells and an aggressive behavior. Immunohistochemically, paragangliomas of the nasal cavity showed increased scores for both proliferation markers tested, indicating a rapid growth pattern. According to the expression of cell-surface markers and oncogene products, these tumors displayed an aggressive behavior and an infiltrating growth pattern. The highest value for the parameters of quantitative DNA analysis and highest proliferation scores were found in a tumor of a patient who developed multiple tumor recurrences after radical excision of the lesion with clear margins, and finally died of disease. In conclusion, paragangliomas of the nasal cavity and paranasal sinuses examined in this study should be regarded as suspicious concerning their biologic and clinical behavior. Radical excision, and in cases with highly aggressive biology, postoperative radiation therapy are recommended. Tumor biologic examinations can help to recognize high-risk patients for developing recurrences and possibly lesions with a malignant behavior and to enhance our understanding of the biology of these extremely rare tumors of the nasal cavity and paranasal sinuses.
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PMID:Biologic characteristics of paragangliomas of the nasal cavity and paranasal sinuses. 1119 19

The aim of this study was to investigate the immunohistochemical expression of the proteins p53, Waf-l/p21, Rb, p16 and Ki67 in 38 cases of multiple myelomas (MM) and 4 cases of solitary extramedullary plasmacytomas in relation to the tumor histological grade and stage. In bone marrow (BM) biopsies from MM, overexpression of p53 and p21 proteins, in comparison to plasma cell infiltrates in non-pathological bone marrow, was detected in 13 out of 38 and 21 out of 38 cases, respectively. The combined immunoexpression of p53 and p21 proteins in the 38 cases of MM showed the following patterns: a) p53+/p21+ (13 cases) b) p53-/p21+ (8 cases) and c) p53-/p21- (17 cases). Rb, p16 and Ki67 proteins were detected in tumor cells in all 38 cases and their expression increased proportionally to tumor grade. The 4 cases of solitary extramedullary plasmacytomas showed the p53+/p21+ pattern in 2 cases and the p53-/p21+ pattern in 2 cases, all of them displaying Rb, p16 and Ki67 expression in tumor cells. The pattern p53+/p21+ might represent cases with wild-type p53 able to induce p21 expression. However, in previous studies p53 mutations were reported in about 3-10% of MM, and they were strongly associated with advanced disease. Thus, in some p53+/p21+ cases associated with high p53 expression and advanced disease, p53 gene cannot be excluded and up-regulation of p21 expression may be p53- independent. P53 overexpression correlated with increased tumor grade (p < 0.005), advanced histological stage (p < 0.001) and Ki67 expression in more than 10% of tumor cells (p < 0.001). Since increase in Ki67 expression also correlated with increased tumor grade (p < 0.001) and advanced histological stage (p < 0.001), these findings suggest that impairment of the p53 growth control pathway is associated with tumor progression in MM. Thus, p53 and Ki67 immunostaining in routine BM biopsies may be helpful for the detection of MM with potentially aggressive behavior. Overexpression of p21 in MM correlated with higher Ki67 expression (p < 0.005), suggesting that the p21 function of arresting cell-cycle is impaired. Ki-67 expression in MM increased in parallel with p16 (p < 0.001) and Rb expression (p < 0.001). Rb expression could represent a growth control response which, however, might not be able to induce growth arrest in view of the parallel increase in Ki67 expression and of previous findings showing that Rb protein in MM cells is expressed mostly in its phosphorylated form.
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PMID:Immunohistochemical expression of the p53, p21/Waf-1, Rb, p16 and Ki67 proteins in multiple myeloma. 1120 12

An 8-year-old girl presented with a cerebral tumor and 3 recurrences within 15 months. The primary tumor was a low-grade astrocytoma, but the recurrences showed progressively malignant phenotypes with increasing mitotic activity and MIB-1 labeling indices. Radiotherapy was given between the first and the second recurrences. Cytogenetic analysis of the first and the second recurrences showed abnormal karyotypes. There seemed to be 2 common breakpoints in these 2 recurrences. TP53 gene mutation screening, using comprehensive denaturing gradient gel electrophoresis, revealed among others a possibly causative mutation of exon 5 in 3 of 4 tumor samples. The meaning of TP53 mutations in low-grade astrocytomas is still unclear, but the highly abnormal karyotypes, which are unusual in these tumors, probably provide genetic evidence for the unexpected aggressive behavior of the tumor in this patient.
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PMID:Recurrent astrocytoma in a child: a report of cytogenetics and TP53 gene mutation screening. 1130 39

Bladder cancer is clinically characterized by a high recurrence rate for superficial tumours up to 70% and by the invasiveness of advanced bladder cancer. To learn more about the biological behaviour of an individual bladder cancer different tumour markers have been investigated. The aim of our study was to compare the potential of aggression of both superficial and invasive bladder tumours by means of the proliferation marker Ki67, the tumour suppressor gene p53, the non metastasizing protein nm23 and the evaluation of DNA ploidy. We examined 36 patients, 28 with a bladder tumour (Ta-T4) and 8 without as a control group. For immunohistochemistry (Ki67, p53, nm23) we took paraffin sections and scored semiquantitatively under a microscope. The DNA cytophotometry was done on bladder washings by evaluating the DNA ploidy of single cells. The results showed that benign tissues were negative for Ki67 and p53 but positive for nm23. The DNA diagnosis was diploid for all benign samples. The superficial bladder cancer (Ta, T1) showed, in comparison to the invasive tumours, significantly lower numbers of aneuploid cells and a higher rate of p53 mutations. On the other hand the invasive tumours (T2-4) were correlated to significantly higher proliferation rates and higher potencies for metastasizing. The combination of the investigated tumour markers allowed a graduation of the biological behavior of an individual bladder cancer. Especially a high p53 mutation rate and a non aneuploid DNA diagnosis were indicators for the recurrence of superficial bladder tumours. Invasive growth of bladder cancer was characterized by high Ki67 proliferation and low nm23 protein binding.
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PMID:Immunohistochemical examinations (Ki67, p53, nm23) and DNA cytophotometry in bladder cancer. 1132 61

This experimental study was designed to evaluate the efficacy of associated naturally occuring antioxidants in the prevention of chemically induced breast cancer using DMBA in virgin female Wistar rats. Rats were randomly allocated to three groups: control group (CG; n = 20), induction group (IG; n = 100), and prevention group (PG; n = 70). A single dose (65 mg/kg) of DMBA was administered in the IG and PG animals at 50 days of age. PG animals also received a single dose of alpha-tocopherol (200 mg/rat) 1 hour after DMBA administration and an association of selenium (p-XSC, 40 ppm/day/rat) and ascorbic acid (540 mg/day/rat) in drinking water, daily, from carcinogenic induction until necropsy. Macroscopic study and pathology revealed a significantly lower development of neoplasms in the PG animals (p < 0.05); the number of rats with mammary tumors, breast cancer incidence, and the number of malignant breast tumors per rat as well as per tumor-bearing rat were significantly decreased in the PG animals. Other types of primary neoplasms existing in the IG animals totally disappeared in the PG animals. Immunostaining to hormone steroid receptors (ER and PR) and cathepsin D was similar in both groups. Overexpression of p53 and metallothioneine was significantly increased in the PG animals (p < 0.05) and immunostaining to bromodeoxiuridin and Ki-67 was also stronger in the remaining tumors in the PG animals. These data thus add to the accumulating evidence that those micronutrients in combination seem to be effective in reducing the incidence of malignant tumors. Nevertheless, remaining tumors seem to present more aggressive behavior and characteristics of drug resistance.
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PMID:Chemoprevention of DMBA-Induced Mammary Tumors in Rats by a Combined Regimen of Alpha-Tocopherol, Selenium, and Ascorbic Acid. 1134 29

Mutation of p53 is rare in localized prostate carcinoma. The oncoprotein MDM2, whose gene has a response element for p53, promotes the degradation of p53 protein and inhibits its transcriptional activation of genes related to cell cycle arrest and apoptosis, constituting a negative feedback control. We studied p53 and MDM2 expression by immunohistochemistry and looked for mutations in p53 exons 5 to 8 by polymerase chain reaction-single strand conformational polymorphism in 118 patients submitted to radical prostatectomy for localized prostate cancer. In 28 cases, we studied cell proliferation by immunohistochemistry, using antibody for Ki-67, and apoptosis by the deoxynucleotidyl transferase mediated dUTP biotin nick end labeling technique. Although no p53 mutations were found, p53 protein was detected in 31.4% of the cases, and these cases had higher Gleason scores (P = .03) and more advanced tumor stages (P = .02). MDM2 was overexpressed in 40.7% of the cases, and these cases had greater tumor volumes (P = .001). Tumors that were positive for both p53 and MDM2 were larger (P = .003) and of more advanced stage (P = .03). Within the 28-case subset, the proliferative index was higher among MDM2-positive tumors (P = .046), and the apoptotic index was lower among p53-positive tumors (P = .01). We conclude that, although p53 mutation is a rare event in prostate carcinogenesis, the detection of p53 protein by immunohistochemistry is common and is associated with decreased apoptosis and increased histologic grade and tumor stage. We also conclude that the overexpression of MDM2 has a role in prostate carcinogenesis, being frequently detected and associated with increased cell proliferation and tumor volume. Finally, we propose that the MDM2-positive/p53-positive phenotype identifies prostate cancers with aggressive behavior.
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PMID:Abnormal expression of MDM2 in prostate carcinoma. 1135 53

Salivary duct carcinoma is an uncommon malignant salivary gland tumor that occurs predominantly in the parotid gland. Oral involvement is extremely rare, with few cases having been reported in the literature. The tumor is characterized by an aggressive behavior and has a poor prognosis. We describe a case of salivary duct carcinoma arising in the hard palate of a 63-year-old man. Immunohistochemical analysis revealed that tumor cells tested positive for cytokeratin, epithelial membrane antigen, proliferating cell nuclear antigen, Ki67, p53, laminin, and collagen IV. Despite radical surgical resection, bilateral neck dissection, and postoperative radiotherapy, liver metastases developed, and the patient subsequently died of his disease.
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PMID:Intraoral salivary duct carcinoma: case report with immunohistochemical observations. 1140 84

We hereby present a retrospective clinicopathological and immunohistochemical study of surgically resected primary gastrointestinal (GI) lymphoma with an analysis of parameters of potential prognostic relevance. From a larger series of 144 cases of primary GI lymphomas, we chose 61 cases with sufficient clinical follow-up (mean 60, range 1-219 months), classified either as extranodal marginal zone B-cell lymphoma of MALT type (MALT lymphoma) or diffuse large B-cell lymphoma (DLBCL), after having excluded other subtypes. In addition to conventional clinical and morphological parameters, the expression levels of Ki-67 (MIB-1), bcl-2 and p53 were evaluated for prognostic significance. Twenty-one (34.4%) cases were classified as pure low grade marginal zone B-cell lymphoma of MALT type, 12 (19.7%) cases as low grade MALT lymphoma with a high grade component (mixed type), and 28 (45.9%) cases as primary extranodal DLBCL. Most of the lymphomas (53/61; 86.9%) were localized in the stomach, 3 (4.9%) in the small bowel, 3 (4.9%) multifocal in both stomach and small intestine and 2 (3.3%) in the large bowel. MIB-1 expression in more than 30% of tumor cells was detected in 42 (68.6%), bcl-2 expression in 20 (32.8%) and p53 accumulation in more than 10% of neoplastic cells in 16 (26.2%) lymphomas. Both high Ki-67 expression and p53 accumulation were more prevalent in the DLBCL. 30 (49%) patients showed lymph node involvement at surgery, 14 (23%) patients suffered tumor recurrence, and 24 (38.5%) died during the follow-up period. Tumor recurrence occurred primarily in patients who had presented lymph node involvement (9/14, 64.3%). The 5-year survival rate was 66.1% for all patients. Important prognostic factors for overall survival were tumor stage (p < .004) and p53 accumulation (p < .05) in univariate analysis, and tumor stage in multivariate analysis (p < .001). Although p53 accumulation did not reach statistical significance in our small study group, it may be both important in the transformation of low grade MALT lymphoma and an indicator for aggressive behavior in high grade tumors.
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PMID:Primary gastrointestinal B-cell lymphoma. A clincopathological and immunohistochemical study of 61 cases with an evaluation of prognostic parameters. 1143 65


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