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 occurrence of primary lung cancer is rare in childhood. The case of an 11-year-old boy with primary lung cancer is presented in this report. He had a substantial family history of cancer. His chief complaint was coughing with right chest pain. A chest radiograph showed a coin lesion in the right lower lung. A right lower lobectomy revealed a squamous cell carcinoma (stage IIIA at Japanese TNM classification). Systemic chemotherapy using cisplatin, vindesine, THP-adriamycin and cyclophosphamide was performed. Six months after surgery, a recurrent tumor occurred. An analysis of the familial cancer related genes (p53 gene and mismatch repair gene) showed no abnormality.
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PMID:Lung cancer in a child with a substantial family history of cancer. 1066 54

Although the mutated p53 gene has been postulated to induce immunohistochemically-detectable p53 protein, reports regarding the relationship between p53 mutation and p53 protein expression have been contradictory. This study investigated the relationship between p53 mutations and p53 expression and their clinical significance for patients with transitional cell carcinoma of the bladder. Eighty-seven transitional cell carcinoma of the bladder were analyzed by immunohistochemistry (IHC) for p53 nuclear accumulation, and the results compared to mutations detected in the p53 gene evaluated by polymerase chain reaction single-strand conformation polymorphism (SSCP) and DNA sequence analysis. By p53 IHC analysis, positive p53 staining was observed in 50 (57.5%) of the 87 tumors. The specificity of IHC, defined as a percentage of IHC negative (<20%) tumors among tumors without mutation, was 94.6%. Despite the good concordance between p53 mutation and p53 protein expression (p<0.0001), 48.0% (24/50) of the tumors showed p53 overexpression without mutation, and 2 (5.4%) tumors with mutation showed no p53 immunoreactivity. Patients with higher grade (grade 3), stage (stages pT2-4), and p53 mutations had a poorer prognosis by Kaplan-Meier survival analysis. A Cox univariate analysis found that grading (hazard ratio 3.139; p=0.002), staging (hazard ratio 3.832; p=0.0005) and p53 mutation (hazard ratio 2.498; p=0.013) were significant variables in these patients, but no variable was independently associated with an increased survival of bladder carcinoma by multivariate analysis. We found that a 20% cut-off level of p53 overexpression showed the highest correlation with prognosis and p53 mutation, however, p53 overexpression and mutation were not superior to staging as prognostic markers. These data suggest that careful assessment of the TNM staging system remains the most reliable predictive indicator of survival for patients with transitional cell carcinoma of the bladder.
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PMID:Relationship between p53 gene mutation and protein expression: clinical significance in transitional cell carcinoma of the bladder. 1067 77

The "new" 3rd WHO classification of lung tumors 1999 is described in nine groups of malignant broncho-pulmonary neoplasias. In recent years, our knowledge of the quite variable biology of tumors has been significantly increased by the use of immunohistochemical methods and molecular biology. These methods facilitated an improved qualitative and quantitative characterization of heterogeneously differentiated long tumors (e.g., neuroendokrine/blastomatoid portions etc.). The detection of genetic alterations of tumor suppressors (Rb/p53/FIHT/TGF beta R-2 etc.) and oncogenes (e.g., myc/fos/blc-2/ras/erbB etc.) is, at the moment, only of scientific interest. The genetic heterogeneity of tumors is emphasized by results obtained with the comparative genomic hybridization (CGH). In small-cell carcinomas of the lung more than seven variable chromosomal alterations--especially loss of genetic material in the regions 3p, 10q, and 4q--can be detected in a tumor. Adenocarcinomas show losses of genetic material on chromosomes 9 and 19, and/or gains on chromosome 1. Squamous cell carcinomas frequently exhibit losses on chromosome 2 and gains on chromosome 3. A connection between the detected genetic anomalies and histomorphological growth patterns can not be seen. At the present time, the validity of individual findings for a correlation between operability, tumor progress, chemotherapy and prognosis is not sufficiently elucidated by investigations nor secured. The histopathological, immunohistochemical, and genetic characterization of specimens of, mostly advanced, lung tumors that show variable phenotypes in biopsies of just 1-2 mm does not allow conclusions regarding causal factors (e.g., smoking, radon, asbestos etc.) or further progress of the disease. Therapeutical approach and the still unfavourable prognosis remain essentially, as in the last thirty years, to be characterized by TNM and performance status of the individual patient and, to a lesser extent, by the main histological type of tumor.
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PMID:[New aspects of lung tumor pathology]. 1071 8

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

Among patients with resected non-small cell lung carcinoma, about 50% will present a tumor recurrence. Thus, it would be of major importance to be able to predict and try to prevent these relapses by an active chemotherapy and/or radiotherapy. In an attempt to answer this question, the tumors of 227 patients with a surgically resected non-small cell lung carcinoma were evaluated as follows: tumors were classified as squamous cell carcinoma (n = 132) or adenocarcinoma (n = 95), and tumor differentiation was evaluated for each type. Then, all tumors were classified in respect to their pathological TNM staging (WHO) and screened by immunohistochemistry for the detection of the expression of the following antigens: Bcl-2, A+B+H blood group antigens, c-erb-b2, p53, and Pan-Ras antigens. Furthermore, adenocarcinomas were screened for the presence of point mutations in Ki-Ras codons 1-31. Finally, the patient blood group was defined, and patient survival was analyzed using nonparametric tests and proportional hazard Cox models. Using Kaplan-Meier survival curves, disease pathological TNM staging was shown to be a strong predictive factor of survival for both squamous cell carcinoma and adenocarcinoma. Patients with squamous cell carcinoma experienced fewer relapses than those with adenocarcinoma (42% versus 63%; P = 0.0002) and had a significantly better survival. All evaluated antigens were more often present in squamous cell carcinoma than in adenocarcinoma except for Pan-Ras (three times more frequent in adenocarcinoma). In patients with squamous cell carcinoma, only tumor staging had a significant prognosis value (P = 0.01). In patients with lung adenocarcinoma, a well-differentiated tumor (P = 0.009) as well as a positive Bcl-2 staining (P = 0.009) and an A+B+H antigen tumor staining (P = 0.024) were associated with a better survival. In contrast, patients with a stage I or II disease and a p53-positive tumor staining and patients with the O blood group (P = 0.01) had a shorter survival. Interestingly, no relation with patient survival was related to c-erb-b2 and Pan-Ras staining. Finally, 12 point mutations were found out of 81 tumors (15%) evaluated for Ki-Ras codons 1-31; they involved codon 12 but also 8, 14, and 15 without any relationship to survival. In respect to lung adenocarcinoma, using Cox proportional hazard models stratified on tumor staging, the following markers were shown to be related to survival: (a) Independent markers of longer survival (ie., high histological degree of tumor differentiation and positive Bcl-2 and A+B+H blood group antigen expression by tumor cells); and (b) Independent markers of shorter survival (i.e., O blood group for all patients and p53 tumor staining in patients with stage I and II diseases). This study suggests that, in patients who undergo surgery for lung adenocarcinoma, the presence or absence of these criteria could be used to define a subset of patients who may benefit from a more specific follow-up.
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PMID:Predictive survival markers in patients with surgically resected non-small cell lung carcinoma. 2667 25

On the subtropical island of Okinawa, squamous cell carcinoma (SCC), particularly the well-differentiated form, is the most frequent type of lung cancer, while this form is relatively rare on the Japanese mainland and in other countries. Furthermore, in Okinawa, in 1993, 80% of SCC cases of the lung were found to be infected with human papillomavirus (HPV). We studied the prognosis of SCC of the lung with HPV infection (n = 25) and compared it with non-HPV-infected SCC (n = 16). Using the Kaplan-Meier method (Wilcoxon analysis), the prognosis of HPV-infected cases was found to be better than that of the non-infected cases. In the virus-infected cases, apoptosis and infiltration of a large number of Langerhans cells were demonstrated. In addition to these findings, the virus-infected tumors were demonstrated to be histologically well-differentiated, perhaps contributing to the favorable prognosis. However, among the virus-infected cases, the type 16 virus-infected cases showed a poorer prognosis, compared to those infected with other HPV types. p53 gene mutation was also examined, and was considered to be an unfavorable prognostic factor, as reported elsewhere. However, in Okinawa, HPV-positive cases with p53 mutations showed a slightly better prognosis than did non-viral infected cases with p53 mutations. The TNM staging system was also useful for categorizing the virus-infected cases. The prognosis of stage III (A and B) cases was poor. All of our present cases received surgical treatment. Chemotherapy and radiation therapy were not performed. Such treatment, however, might be effective, because virus-infected uterine cervical carcinomas have been routinely treated with chemotherapy and radiation. Furthermore, if the immunological basis of increased Langerhans cell infiltration in HPV-infected cases is elucidated, a clinical trial with immunotherapy may be favorable for the clinical outcome.
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PMID:Prognostic implication of human papillomavirus infection in squamous cell carcinoma of the lung. 1078 64

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 is one of the downstream target genes for transcriptional activation by the product of the p53 tumor-suppressor gene. Transactivation of MDM2 gene expression is represented by the presence of a functional p53 protein. We hypothesized that MDM2 mRNA expression may be a more suitable prognostic factor than p53 or MDM2 protein expression and p53 gene mutations. In this study, expression of MDM2 mRNA, p53 protein, and MDM2 protein and mutations of the p53 gene were assessed in 81 lung tumor tissue specimens using RT-PCR, immunohistochemistry, and direct sequencing among exons 5-8, respectively. By immunohistochemistry, 33 and 42 of 81 patients with p53 (40.7%) and MDM2 (51.5%) protein expression were found in lung tumor specimens, respectively. The p53 direct sequencing data indicated that 13 of 81 patients (16.0%) had p53 mutations. However, Kaplan-Meier analysis showed that p53 protein and MDM2 protein expression and p53 mutation were not useful as prognostic factors. Interestingly, the survival of patients with MDM2 mRNA expression was longer than that of patients without MDM2 mRNA expression, though MDM2 mRNA expression was not associated with clinicopathological parameters, including tumor grade, tumor stage, tumor type, and TNM values. Moreover, Cox regression analysis showed that MDM2 mRNA expression was a significantly independent favorable prognostic factor in non-small-cell lung cancer (NSCLC) patients. Thus, measuring MDM2 mRNA expression using RT-PCR may be a simple, useful approach for predicting the survival of NSCLC patients.
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PMID:MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer. 1086 3

Mutations in the p53 gene--which codifies anuclear phosphoprotein that acts as a tumor suppressor gene--is the most common genetic alteration in head and neck cancers. The aim of the present study was to investigate the prognostic significance of p53 protein over expression in squamous cell laryngeal carcinoma. To do so we analyzed 31 patients affected by precancerous lesions of the larynx who had undergone multiple biopsy between 1980 and 1995. Twenty-five of these patients later developed laryngeal carcinoma. In this group of patients, 51 biopsies were performed for precancerous lesions (17 hyperplasia, 3 light dysplasia, 23 moderate dysplasia, 8 severe dysplasia) prior to evidence of laryngeal cancer (2.04 biopsies/patient). In the group of patients who did not develop laryngeal cancer, 18 biopsy were performed (2.2 biopsies/patient) and histology revealed: 5 keratosis, 5 light dysplasia, 4 moderate dysplasia and 4 grave dysplasia. Using the immunohistopathological staining technique, 69 formalin-fixed, paraffin-embedded precancerous samples and 25 laryngeal carcinomas were examined for p53 over expression. The monoclonal antibody Pab 1801 was used with the avidinbiotin immunoperoxidase technique; p53 intensity of expression was assessed and correlated with clinical-pathological parameters. Over expression of the p53 protein was found in 56.8% of the precancerous lesions (41% of the hyperplastic lesions, 66% of light dysplastic lesions, 60% of moderate dysplastic lesions and 75% of severe dysplastic lesions) in the group patients who did develop laryngeal cancer and in 22.2% of the precancerous lesions in the group of patients that did not. The transformed lesions showed a strong correlation between intensity of positivity and grade of cellular atypia. Further in 93.3% of the patients with p53 positive precancerous lesions which later developed into laryngeal cancer, p53 over expression was present in the cancerous lesions. There was no significant correlation between p53 immuno reactivity and such clinico pathological tumor parameters as TNM staging and tumorrecurrence. On the other hand, there was a correlation between p53 overexpression and differentiation grading: p53 overexpression was found in 75% of the poorly differentiated tumors, 58.3% of moderately differentiated and 44.4% of well differentiated tumors. The fact that p53 is detected in preneoplastic lesions suggests that p53 gene alteration takes place very early in laryngeal carcinoma and moderate-to-high p53 expression constitutes a high risk of transformation into cancer; on the other hand low expression may reflect reversible changes that can be attributed to the genotoxic effects of tobacco smoking. In conclusion the present data suggest that p53 over expression could be a good prognostic marker in predicting which precancerous laryngeal lesions will progress into cancer.
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PMID:[The role of p53 tumor suppressor gene as prognostic factor in laryngeal squamous cell carcinoma]. 1087 57

The incidence of and mortality from squamous cell carcinoma (SCC) of the tongue have increased during the recent decades in the Western world. Much effort has been made to predict tumour behaviour, but we still lack specific prognostic indicators. The aim of our study was to evaluate the relative importance of the known demographic, clinical and histological factors in a homogeneous population-based group of patients with SCC of the mobile tongue. The demographic and clinical factors were reviewed retrospectively from primary and tertiary care patient files. Histological prognostic factors were determined from pre-treatment biopsies. The TNM stage was found to be the most important prognostic factor. In particular, local spread outside the tongue rather than spread to regional lymph nodes was related to poor prognosis. Several demographic and histopathological factors were closely related to TNM stage. When the cases were divided into stage I-II carcinomas and stage III-IV carcinomas, it appeared that the patient's older age (> 65 years), a high malignancy score and an absence of overexpressed p53 protein were associated with a poorer prognosis in stage I-II carcinomas. Such cases may require more aggressive treatment. Among patients with stage III-IV carcinomas, heavy use of alcohol was significantly associated with a poor disease-specific survival time.
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PMID:Prognostic factors in tongue cancer - relative importance of demographic, clinical and histopathological factors. 1094 1


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