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)

In addition to the tumor suppressor gene p53, Cyclin Dependent Kinases (CDK) are well known to influence the cell cycle in normal human tissues and various neoplasias as well. The purpose of our present study was to evaluate the expression of the CDK-inhibitor p21/waf1/cip1 in colorectal cancer with special emphasis on the prognostic impact. Between 1985 and 1991, 294 patients (median age, 65 years) underwent surgical operative therapy for colorectal cancer. Formalin-fixed and paraffin-embedded tumor specimens were investigated. For immunohistochemistry the Catalysed Reporter Deposition (CARD) technique was performed. The survival probability was calculated and possible prognostic risk factors were tested using multivariate analysis. The p21/ waf1/cip1 staining pattern was positive in 197 (67%) specimens and negative in 97 (33%) samples. No significant correlation could been calculated between p21/waf1/cip1 expression and other variables such as age, sex, WHO-Classification, localisation, grading, TNM-classification or UICC-stage. Patients with a positive staining reaction had a significantly better survival (p < 0.0052). Moreover, p21/waf1/cip1 was shown to be an independent prognostic parameter by multivariate analysis (p < 0.022). In contrast with these findings, the p53 tumor status had no impact on survival. P21/ waf1/cip1 appears to be an independent prognostic parameter in colorectal cancer and is associated with a favorable survival. This feature may be related to a cell cycle arrest in the G1 phase induced by p21/waf1/cip1, resulting in lower tumor cell proliferative activity.
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PMID:Prognostic impact of p21/waf1/cip1 in colorectal cancer. 1071 25

The aim of the present study was the evaluation of the immunohistochemical expression of the apoptosis-inhibiting protein bcl-2, the cell-cycle-related antigen Ki-67 and the p53 protein, which is involved both in cell cycle and apoptosis regulation, in the lining epithelium of glandular odontogenic cysts of the jaws. Formalin-fixed and paraffin-embedded tissue sections of three glandular odontogenic cysts and six dentigerous cysts were immunostained with a standard avidin-biotin peroxidase procedure, after microwave antigen retrieval. The glandular odontogenic cysts showed immunoreactivity for bcl-2 protein in the basal and suprabasal layers, while staining in dentigerous cysts was basal or focal. Most mucous cells and superficial cuboidal cells were negative. The percentage of Ki-67- or p53-positive cells was lower in glandular odontogenic cysts compared with dentigerous cysts. The findings suggest that the biological behavior of glandular odontogenic cysts may be associated with deregulation of cell death in the lining epithelium, while cell proliferation and p53 status do not seem to play a significant role.
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PMID:Immunohistochemical study of bcl-2 protein, Ki-67 antigen and p53 protein in epithelium of glandular odontogenic cysts and dentigerous cysts. 1073 41

The prognostic role of ploidy status, S phase fraction, estrogen and progesterone receptor status, and the expression of p53 and erbB-2 protein in male breast carcinoma (MBC) remains controversial. The primary objective of this study was to determine which of the common prognostic factors for female breast cancer predict prognosis in MBC. A secondary objective was to assess the impact of comorbid illnesses on survival. A retrospective review of demographic data, surgical treatment, pathological staging, adjuvant treatment and follow-up was completed for 16 patients with MBC (1 intraductal and 15 invasive). Formalin-fixed, paraffin-embedded tissue was processed for ploidy, S phase fraction, and immunohistochemical detection of estrogen and progesterone receptors plus expression of p53 and erbB-2 protein. Six of 15 patients with infiltrating ductal carcinoma are currently alive without evidence of disease and a median survival of 61 months. Nine patients died after a median survival of 52 months, with 6 patients having no evidence of recurrent breast cancer. Two of 3 deaths secondary to advanced breast cancer occurred in patients who initially presented with T4 lesions and were staged IIIB. Two of 15 tumors were erbB-2 positive, whereas only 1 tested weakly positive for p53 protein. We observed that MBCs express erbB-2 and p53 proteins infrequently. Neither ploidy status, S phase fraction, nor erbB-2/p53 status provided any apparent improvement in establishing prognosis beyond routine pathological staging. Advanced TNM stage was associated with diminished survival. The majority of MBCs express estrogen and progesterone receptors. Survivals in MBC were reduced in association with comorbid medical conditions.
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PMID:Prognostic variables in male breast cancer. 1082 54

Mdm2 protein is a cellular regulator of p53 protein activity. Minor salivary gland tumours were investigated for immunohistochemical expression of Mdm2 protein and for p53 gene status. Formalin-fixed sections were submitted to monoclonal antibody anti-Mdm2 through use of the streptavidin-biotin method. Nuclear immunoreactivity was scored 1 (0-25% nuclei positive), 2 (26-50%), 3 (51-75%) and 4 (> 75%). The scores found were: PLGA = 1-4; ACC = 3 and 4; ACA = 2 and 4; PA = 3. Genomic DNA of p53 gene exons 5-8 was examined by polymerase chain reaction and no alterations were detected. The strong immunohistochemical Mdm2 expression may represent an alternative mechanism to the development of salivary gland tumours.
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PMID:Immunohistochemical Mdm2 expression in minor salivary gland tumours and its relationship to p53 gene status. 1088 22

Various recognized prognostic factors in squamous cell carcinoma (SCC) of the larynx influence the therapeutic options offered to an individual patient in order to extend the survival expectancy. Additional prognostic indicators are required in specific patient subgroups. The present study used a standard immunohistochemical technique in order to retrospectively evaluate the accumulation of p53 gene product and the immunoreactivity of bcl-2 protein and cathepsin-D as possible prognostic markers of laryngeal SCC. Formalin-fixed, paraffin-embedded tumor materials were obtained from a series of 64 patients with cancer of the larynx. Immunostaining was evaluated by computerized image analysis. The accumulation of p53 protein was found in 57.8% (37/64) of the patients and was associated with large tumor size. The percentage of p53-positive neoplastic cells increased in high-grade carcinomas, particularly when they simultaneously demonstrated cathepsin-D immunoreaction in stromal cells (P = 0.049); bcl-2 immunoexpression was found to be generally limited. Cathepsin-D immunostaining was observed in tumor parenchymal and stromal cells (31.25% and 37.5% of all cases, respectively); it was found to be useful in defining patient subgroups with differences in relapse-free survival. Among patients with posi-tive lymph nodes, those with cathepsin-D immunopositive tumor cells were at higher risk for relapsing (P = 0.0395). Although the classical prognostic factors of laryngeal carcinoma retain their predominance, cathepsin-D immunoreactivity may serve as an additional prognosticator in specific patient subgroups.
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PMID:Correlation of tumor markers p53, bcl-2 and cathepsin-D with clinicopathologic features and disease-free survival in laryngeal squamous cell carcinoma. 1101 85

Loss of p53 function has been implicated in a wide variety of human malignacies. Many studies suggest that in cervical carcinoma p53 function is inactivated either by gene mutation or by complex formation with E6 oncoprotein product of high-risk human papillomavirus (HPV). The aim of this study was to determine the status of HPV infection and p53 gene mutation as well as their correlation in cervical carcinomas. Formalin-fixed paraffin-embedded tissues of 12 cervicitis, 21 cervical intraepithelial neoplasia grade 3 (CIN 3) and 17 squamous cell carcinomas were determined for the presence of HPV using polymerase chain reaction (PCR) amplification and dot blot hybridization. The status of p53 mutations in exons 5-8 was evaluated by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and confirmed by direct nucleotide sequencing. HPV infections were detected in all CIN 3 and squamous cell carcinomas (100%). Mutations of p53 were present in 3 of 38 HPV-positive samples: one with an ATG-->TTG transversion (Met-->Leu) in codon 237 of exon 7; and the others with a TGC-->TGG transversion (Cys-->Trp) in codon 242 of exon 7, and a CGT-->CCT transversion (Arg-->Pro) in codon 273 of exon 8, respectively. Our findings show that the frequency of p53 mutation is low in primary cervical carcinoma and that the p53 gene mutation and HPV infection are not mutually exclusive events in the development of cervical cancer. Thus, other genetic events independent of p53 inactivation may also significantly contribute to the carcinogenesis of the uterine cervix.
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PMID:p53 status and human papillomavirus infection in Thai women with cervical carcinoma. 1102 67

The aim of the study was to examine the relation between p53 protein accumulation, clinicopathological variables and prognosis in resectable adenocarcinomas of the pancreatic head. The clinical records and tissue specimens of 82 consecutive patients resected for adenocarcinomas located in the head of the pancreas were reviewed retrospectively. Formalin-fixed and paraffin-embedded specimens from each tumour were stained with the monoclonal antibody DO7, and the nuclear p53 positivity within each tumour was assessed. Histopathological reclassification showed that 60 tumours exhibited ductal differentiation and 22 tumours intestinal differentiation. Twenty-five percent (15/60) of the ductal tumours and 50% (11/22) of the intestinal tumours were positive for p53 accumulation. p53 immunoreactivity was significantly correlated to a worse prognosis in the tumours of ductal differentiation, with median survival 0.76 years for p53 positive and 1.44 years for p53 negative patients. The p53 positivity of tumours with intestinal differentiation showed no such correlation. No correlation was found between p53 accumulation and other known prognostic factors in either the ductal or the intestinal type of tumours. Our results indicate that the tumour biology of ductal adenocarcinomas differs significantly from that of adenocarcinomas of the intestinal type located in the pancreatic head, and that p53 accumulation confers a worse prognosis only of ductal tumours. Subclassification of these tumours based on type of differentiation is therefore suggested since periampullary tumours include ductally as well as intestinally differentiated adenocarcinomas.
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PMID:p53 accumulation confers prognostic information in resectable adenocarcinomas with ductal but not with intestinal differentiation in the pancreatic head. 1102 93

Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. Our aim was to undertake a comprehensive analysis of potentially useful molecular markers in a large, multicentre patient population and to compare these markers with standard pathological prognostic variables. Formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients [100 men and 57 women with a median (range) age of 60 (33-77) years] who had undergone pancreatectomy. Immunohistochemistry was used to detect expression of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3. Mutations in codons 12 and 13 of the K-ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median (range) survival post-resection was 12.5 (3-83) months. Abnormalities of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K-ras mutations were found in 73 (75%) of 97 cases with amplifiable DNA. The presence of K-ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K-ras mutation (p = 0.0007). Reduced survival was found in patients with GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion, survival was associated with type of K-ras mutation but not expression of p16(INK4), p53, p21(WAF1), cyclin D1, erbB-2 and erbB-3.
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PMID:K-ras oncogene subtype mutations are associated with survival but not expression of p53, p16(INK4A), p21(WAF-1), cyclin D1, erbB-2 and erbB-3 in resected pancreatic ductal adenocarcinoma. 1110 89

Formalin fixed and paraffin embedded samples from 36 squamous cell carcinomas of the larynx and the oral cavity (pT2N0M0, R0) surrounded by non-tumorous mucosa were studied immunohistochemically using a panel of four different anti-p53 antibodies (CM1, PAb1801, D07, PAb240), a monoclonal anti-mdm2 antibody and MIB1, following wet autoclave antigen retrieval. P53 immunoreactivity was detected in 11/14 laryngeal and in 9/22 oral carcinomas. All p53 positive oral, and all but one laryngeal tumors revealed mdm2 positivity as well, whereas in p53 negative tumors 4/12 and 1/3 mdm2 immunopositive cases were demonstrated, respectively. MIB1 labeling indices of the tumors ranged between 18% - 64% in p53 positive cases, and 10% - 53% in p53 negative ones. The difference was not statistically significant. Close spatial coexpression of p53, mdm2 and MIB1 immunoreactivity was observed at the invasive front of the carcinomas and in the basal and suprabasal layers of the non-tumorous epithelium in all p53 positive cases. However, the MIB1 expression was similarly increased at the invasive margins in carcinomas lacking immunohistochemically detectable p53 alterations. Our results strongly suggest that p53 overexpression does not necessarily correspond to increased rate of proliferation, but rather to mdm2 overexpression and is largely dependent on the anatomical site in case of small and localized squamous cell carcinomas of the head and neck region.
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PMID:Proliferative (MIB1, mdm2) Versus Anti-Proliferative (p53) Markers in Head and Neck Cancer. An Immunohistochemical Study. 1117 81

The observation that p53 alterations are early events in the tumorigenesis of head and neck cancer and the association with cigarette smoking have prompted us to search for p53 overexpression in the oral mucosa of heavy smokers who have no overt precancerous or cancerous lesions. Formalin-fixed paraffin embedded tissue sections, obtained from oral mucosa of 30 otherwise healthy heavy smokers, were evaluated for tobacco related changes, and immunostained with a mouse monoclonal antibody p53-DO7 for p53 immunoreactivity. Histopathological evaluation revealed hyperplastic changes in twenty eight samples (93%), eight of which also demonstrated dysplastic changes. Positive immunoreaction for p53 was detected in six (20%) of the tissue samples. The study provided significant information about the frequency of hyperplasia, dysplasia, and p53 overexpression in individuals who were heavy smokers. It is suggested, also, that chemoprevention might have some impact in this particular group of individuals.
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PMID:P53 overexpression in normal oral mucosa of heavy smokers. 1127 33


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