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)

Bowen's disease is a premalignant dermatosis comprised of a clonal proliferation of atypical keratinocytes in the full thickness of the epidermis. To elucidate the relationship between the alteration of the p53 tumor suppressor protein and cell proliferation rate, we immunohistochemically examined the expression of proliferating cell nuclear antigen (PCNA) and p53 protein in 30 cases of Bowen's disease. All the cases exhibited the full-thickness distribution of PCNA-positive cycling cells in the lesional epidermis. Quantitation of PCNA staining by image cytometry revealed a mean labeling index (LI) of 75.1 +/- 20.3. p53 expression was detected in 13 cases (43%). Expression was diffuse (p53 LI > 50) in 9 cases, but focal (p53 LI < 30) in the other four. The mean PCNA LI of p53 diffusely positive cases was significantly greater than that of both p53 focally positive and p53 negative cases (89.3 +/- 10.1 vs 62.7 +/- 21.2, and 70.5 +/- 21.6; p < 0.01, respectively). These findings suggest that a high-level accumulation of p53 protein results in a more increased cell proliferation in Bowen's disease.
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PMID:Proliferating cell nuclear antigen (PCNA) and p53 protein expression in Bowen's disease. 786 67

Because therapeutic efforts such as surgery, radiotherapy, and chemotherapy have only marginally improved the 5-year survival rate from cancers of the upper aerodigestive tract (including head and neck and lung cancers) over the past 2 decades, chemoprevention has become an important strategy in reducing the rates of incidence and mortality of these cancers. However, chemoprevention trials have been hampered by serious feasibility problems; they require large numbers of subjects and long-term follow-up for accurate determination of cancer incidence and they are very costly. Because the use of intermediate end points would reduce the duration and costs of these studies, biomarkers that could serve as such end points have recently become a subject of great interest. With the strengthening of the assumption that tumorigenesis is a multistep process of transformation from normal tissues to malignant lesions, there has been a great effort to examine each of these steps for genetic and/or phenotypic alterations that might be candidates for such biomarkers. These candidates include genomic markers, certain specific gene alterations, such as tumor suppressor genes, oncogenes, growth factors and their receptors, proliferation markers, and differentiation markers. In this review, we describe several genomic markers, including micronuclei, chromosomal alterations, and specific genetic markers, e.g., the ras gene family, erb B1, int-2/hst-1, and p53 tumor suppressor gene. We also review the proliferation markers, including proliferating cell nuclear antigen, and squamous cell differentiation markers, including keratins, involucrin, and transglutaminase 1. These biomarker candidates have the potential to be important adjuncts to the development of new chemopreventive agents and to the rational design of future intervention trials. However, we can not overemphasize that these markers need to be validated in clinical trials; only then can they replace cancer incidence as the sole end point for chemoprevention trials.
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PMID:Biomarkers in upper aerodigestive tract tumorigenesis: a review. 788 44

For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumor-suppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of P53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications. 788 74

Forty-nine follicular adenomas and 11 follicular carcinomas of the thyroid were investigated by immunohistochemistry for the expression of p53 protein and proliferating cell nuclear antigen (PCNA). The DNA ploidy and the S-phase fraction (SPF) of the neoplasms were analysed by flow cytometry. Twelve adenomas (24 per cent) and six carcinomas (55 per cent) were DNA non-diploid (P = 0.07). The carcinomas had a higher proliferation rate than the adenomas when assessed either by SPF size (median 9.9 per cent vs. 2.9 per cent, P = 0.0003) or by PCNA staining intensity (P < 0.0001). Some scattered nuclei in two (4 per cent) adenomas and in three (27 per cent) carcinomas stained positively for p53 (P = 0.04). The two adenomas with positive staining for p53 were subserially sectioned, but no signs of invasion were found; both patients are alive and well 6 and 7 years after surgery. One of the two adenomas showing positive p53 nuclear staining was DNA aneuploid, and both were positive in PCNA staining, but their SPFs were low (2.1 and 3.3 per cent). We conclude that p53 protein expression is not confined to follicular carcinomas; scattered p53-positive cells may also be present in histologically and clinically benign follicular adenomas. Because both follicular adenomas and carcinomas may be DNA aneuploid and their SPF and PCNA staining distributions overlap, the distinction between follicular adenoma and carcinoma should still be based on histological criteria.
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PMID:p53 protein, PCNA staining, and DNA content in follicular neoplasms of the thyroid gland. 788 88

Mutation in the p53 tumor suppressor gene is the most common genetic alteration in human cancer. As in mutant p53 the protein is stabilised and the half-life is extended, it becomes detectable by immunohistological staining. p53 immunoreactivity thus seems to be a potential biomarker for the assessment of the oncogenic potential of malignant melanomas. In 103 tissue sections of primary and metastatic malignant melanomas of the head and neck detectable levels of p53 were only found in 3 of the primary tumors and in none of the metastases. At the same time the proliferation status of the malignant melanoma lesions was determined using the cell cycle specific antibody PCNA. 55 primary and metastatic tumors were stained with a PCNA-MAb to determine the proliferation activity of the tumors. The results of our immunohistochemical investigation suggest that immunoreactivity of p53 cannot be used to determine the malignant potential of melanomas in the head and neck. PCNA staining showed that the majority of the tumors and metastases were proliferating rapidly.
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PMID:p53 and PCNA expression in malignant melanomas of the head and neck. 788 8

Paraffin-embedded surgical specimens from 56 human astrocytomas (8 pilocytic [I degree] astrocytomas, 9 low grade [II degrees] fibrillary astrocytomas, 9 high grade [III degrees] astrocytomas and 30 glioblastomas) were immunostained with the anti-PCNA, anti-p53, anti-Ki-67 and anti EGFR antibodies. Approximately 41% of all cases were p53 protein-positive while 23% were EGFR positive. Five cases (8.9%) were positive for both p53 protein and EGFR. Low grade gliomas showed low PCNA LI while high PCNA LI was observed in high grade gliomas. The same trend was observed with anti-Ki-67 antibodies but the proportion of Ki-67 immunolabelled cells was always much lower. In conclusion, we found two populations of astrocytic tumors with EGFR and with p53 protein overexpression but no dependence between p53 immunoreactivity and PCNA or Ki-67 LI.
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PMID:Expression of p53-protein, epidermal growth factor receptor (EGFR) and proliferating cell antigens in human gliomas. 788 34

In an immunohistochemical study of 490 primary breast cancer patients with a follow-up period of more than 10 years, we found that p53 was not a prognostic factor for disease-free or overall survival among the whole cohort or among lymph node-positive or -negative patients. In a multiple logistic regression model classical histopathological parameters, such as lymph node status, number of mitoses, histological grade, and absence of progesterone receptors, were independent, poor prognostic predictors. In univeriate analysis p53 immunoreactivity was positively correlated with the absence of tubule formation, high histological grade (poor differentiation), absence of estrogen receptors (ER), and a high proliferating cell nuclear antigen (PCNA) score (ie, parameters indicative of an aggressive phenotype). The lack of prognostic significance may be attributable partly to the method used, because immunohistochemistry underdetects rather than overdetects p53 protein. No correlation between p53 and c-erbB-2-oncoprotein was demonstrated.
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PMID:An immunohistochemical study of p53 with correlations to histopathological parameters, c-erbB-2, proliferating cell nuclear antigen, and prognosis. 789 Feb 81

Thirty-eight cases of pancreatic duct cell carcinoma were examined for p53 expression and proliferating cell nuclear antigen (PCNA) by enhanced immunohistochemistry, as well as for changes in numbers of argyrophilic nucleolar organizer regions (AgNORs). Fifteen cases (39.5%) showed p53 overexpression, which tended to increase in proportion to the histopathological grading of malignancy. However, tumor stage and lymph node status were not correlated to p53 overexpression. PCNA labeling index (LI) increased with both histologically malignant grading and pathological stage, but was not correlated with lymph node status. The expression of p53 and PCNA thus did not necessarily reflect the degree of malignant development. In contrast, AgNOR number showed statistically significant correlations with these three indicators of malignancy. A comparative analysis of p53, PCNA LI and AgNOR number showed overexpression of p53 to be correlated to PCNA LI and essentially unrelated to AgNOR number. The present results thus indicate a close relation between p53 and PCNA, while AgNORs appear to be regulated separately from either of them.
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PMID:Comparative immunohistochemical studies of p53 and proliferating cell nuclear antigen expression and argyrophilic nucleolar organizer regions in pancreatic duct cell carcinomas. 790 Nov 90

Forty oral squamous cell carcinomas and 20 leukoplakias were examined for expression of p53 oncoprotein using an immunohistochemical technique with BP53-12 monoclonal antibody. Positive staining was found in 21/40 (52%) of the carcinomas and 2/20 (10%) of the leukoplakias. Furthermore, comparison of p53 expression with binding of PC10 monoclonal antibody to proliferating cell nuclear antigen (PCNA) and degree of histological malignancy in terms of invasion and histological differentiation of carcinomas demonstrated a positive correlation in both cases.
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PMID:Immunohistochemical detection of p53 oncoprotein in human oral squamous cell carcinomas and leukoplakias: comparison with proliferating cell nuclear antigen staining and correlation with clinicopathological findings. 790 26

Squamous epithelial cancer in situ (CIS) of the upper aerodigastric tract is a histopathologically well-defined condition. However, in clinical practice, morphological grading of dysplasia is difficult and shows large variability. The biology of CIS remains enigmatic, and there is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed image DNA cytometry (ICM) and immunohistochemical staining for PCNA as well as p53 in 38 laryngeal CIS lesions, of which 9 progressed to invasive cancer. The majority of the CIS lesions displayed high-grade DNA aberration, a high PCNA-positive rate, and every third lesion was p53-positive by immunostaining. The lesions which progressed to invasive cancer showed a clear tendency towards more pronounced DNA aberration, a higher percentage of intense PCNA staining and more frequent p53 positivity. By combining the results from the analyses of DNA, PCNA and p53 in a prognostic index for each individual case, we correctly classified 82% of the lesions as progressors or non-progressors.
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PMID:Nuclear DNA content, proliferating-cell nuclear antigen (PCNA) and p53 immunostaining in predicting progression of laryngeal cancer in situ lesions. 790 88


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