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 protein p53 is a product of a suppressor oncogene. Mutations occurring in 13-15% of breast carcinomas are associated with p53 stainability within nuclei and progression of the tumor. We determined the extent to which p53 abnormality was associated with proliferation by measuring p53 immunohistochemically with a polyclonal antibody and monoclonal PAb1801 in invasive carcinomas of known S-phase fraction (SPF) assessed histologically by bromodeoxyuridine incorporation. Results with the two antibodies always agreed. One of 20 low, 2/18 midrange, and 9/17 high SPF carcinomas were positive for p53. P53 positivity was also related to other indicators of aggressiveness including size of primary tumor, nuclear and nucleolar size, and estrogen and progesterone receptor content, but relationships between p53 and vascular invasion and lymph node metastasis were not found. We conclude that nuclear p53 accumulation is more closely related to proliferation than to invasion and metastasis, and that it identifies some but not all breast carcinomas with high proliferative indices.
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PMID:High proliferative rates demonstrated by bromodeoxyuridine labeling index in breast carcinomas with p53 overexpression. 802 44

P53 protein in cutaneous melanoma. We report the results of an immunohistochemical analysis about the nuclear phosphoprotein P53 expression performed on 48 primary and 10 metastatic cutaneous melanoma in order to assess the prevalence of the expression of mutant P53 protein (m-P53) in this skin tumour. In our study m-P53 was found in about 46% of primary tumours without any significant relationship with the corresponding metastatic lesions. Therefore the P53 count in cutaneous melanoma is not a prognostic marker of tumour spread and aggressiveness.
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PMID:[Expression of P53 protein in cutaneous melanoma]. 823 50

The recent advances in molecular biology have led to a concept that carcinomas arise from the accumulation of a series of genetic alterations involving activation of protooncogenes and inactivation of tumor suppressor genes. The present study was designed to elucidate that such processes take place in the tumorigenesis of the uterine endometrium as well. The incidence of ras gene mutation, which were mostly composed of the point mutations of k-ras codons 12 and 13, was higher in carcinomas (31%) than atypical hyperplasias (15%), with marginal significance, but has not been associated with aggressiveness of the carcinomas. Thus, k-ras activations may occur as an early event in tumorigenesis. Mutations of tumor suppressor gene, p53, were detected in 24% of carcinomas and 8% of atypical hyperplasia, while they are not statistically different. The p53 mutations were associated with poorly differentiated adenocarcinomas. The most common pattern of the base change detected in endometrial carcinomas was the transition from G:C to A:T. The p53 mutations at CpG sites were frequent, especially at codon 248. Loss of heterozygosity (LOH) was more frequently detected than the mutations and most cases with LOH harbored the mutations, suggesting that allelic loss may precede the mutation in the tumorigenesis of endometrium. Expression of p53 was well correlated with type of the p53 mutation and its overexpression is associated with aggressive clinical behavior, suggesting the possible application of p53 as a prognostic indicator. The other tumor suppressor genes, Retinoblastoma gene (RB) and DCC gene, were also involved in the endometrial carcinogenesis. LOH and abnormal m-RNA of RB were detected in 15% and 33% of carcinomas, respectively, and associated with advanced clinical stage and poorly differentiated adenocarcinomas. LOH of DCC was also detected in some cases while that of APC was not detected. Thus, tumor suppressor genes may also play an important role as later events in carcinogenesis by inactivation mechanism consisting of the loss of one chromosomal allele and/or mutation of the gene in the remaining allele. Human papillomavirus (HPV) DNA type 16 was curiously detected in 5% of cases by both Southern blot and in situ hybridization analyses. Consequently, two third of endometrial carcinomas examined in the present study for ras, p53, RB, DCC, APC and HPV showed abnormality of at least one of these genes. The abnormality of multiple genes may contribute as an etiologic role to multisteps in carcinogenesis of the endometrium.
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PMID:[Genetic alterations and transformations in development and establishment of uterine endometrial carcinomas]. 837 Oct 6

Striking differences were found between different histological types of breast cancer when 263 invasive breast carcinomas were tested for nuclear p53 accumulation in formaldehyde-fixed paraffin sections. Nuclear p53 accumulation was found in > 10% of tumor cells in 61% of medullary carcinomas (22/36), 37% of grade 3 ductal not otherwise specified carcinomas (32/86), 4% of lobular carcinomas (2/47), and 0% (0/7) of mucinous carcinomas. Strong cytoplasmic p53 staining was noted in 32% of lobular carcinomas. High percentages of medullary and high-grade ductal breast carcinomas accumulate nuclear p53, but these tumors have favorable and poor prognoses, respectively. Thus, whereas nuclear p53 accumulation can be associated in these tumors with high morphological malignancy grades in general and with tumor cell proliferation in particular, p53 accumulation is not necessarily correlated with biological aggressiveness. Overall incidence of p53-positive tumors in a particular series of breast carcinomas (in our study 28%) will depend on the ratio of ductal not otherwise specified, medullary, and lobular carcinomas.
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PMID:Nuclear p53 protein accumulates preferentially in medullary and high-grade ductal but rarely in lobular breast carcinomas. 829 10

Alterations of p53 are one of the most common molecular changes found in all types of lung tumors, suggesting a crucial role for p53 in bronchial carcinogenesis. However, the prognostic significance of p53 abnormalities in lung cancer patients is still unclear. By using genetic and immunohistochemical methods we have found p53 alterations in 40 of 53 (75%) primary, resected non-small cell lung cancer. A strong association (P = 0.0015) was found between deletions on chromosome region 17p13.3 and p53 mutations suggesting that loss of the wild-type p53 allele might be necessary for tumorigenesis. Correlations to clinicopathological parameters showed that p53 alterations (structural aberration of the gene and/or nuclear accumulation of the protein) are significantly linked with metastatic involvement of hilar and mediastinal lymph nodes (P < 0.01). Since the latter are well established prognostic factors for non-small cell lung cancer, p53 aberrations may also be a predictor of tumor aggressiveness.
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PMID:p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes. 838 45

In this article the results of molecular marker p53 examinations were presented in relation to the following established breast cancer prognostic factors: age, histologic type, histologic grade, lymph node involvement, tumor size as well as estrogen a progesterone receptor status. Twenty one percent of these primary breast cancer specimens exhibited the overexpression of p53 protein. Significant associations were found between p53 overexpression and younger age, high histologic grade and low content of estrogen and progesterone receptors. Identification of p53-positive breast carcinomas potentially represents a clinically useful indicator of breast cancer aggressiveness.
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PMID:p53 expression in breast cancer related to prognostic factors. 855 1

The pattern of p53 protein expression was examined in 92 cases of thyroid carcinoma. When the cases were divided into two groups with regard to their cytoplasmic staining only or nucleus staining only, the frequency of the nucleus staining group was significantly higher in the poorly differentiated carcinoma (PDC) and undifferentiated carcinoma (UDC) groups (10.5% and 25%) compared with the other groups of histologic subtype (0%). The results suggest positivity in nucleus staining for p53 may be a marker for the biologically worse carcinomas, PDC and UDC, however, tumors showing only cytoplasmic staining of p53 favor a fair prognosis. In this paper, we also elucidate the spectrum of genotypic aberrations of p53 in each histological subtype. Of 92 thyroid tumor samples analyzed, the overall frequency of p53 mutation was 8.5%. The mutations occurred in 4.35% (2/46) ot WDC, 17.2% (5/29) of PDC, and 16.7% (1/6) of oncocytic carcinoma. Two of five PDC cases and one papillary carcinoma revealed point mutations in exon 8 as follows; GTG (val) to CTG (leu) at codon 272 in case 23T, CGA (arg) to CCA (pro) at codon 306 in case of 30T, and CGG (arg) to AGG (arg) at codon 282 in case 28T. All of the p53 mutations detected were represented by single nucleotide changes including two missense and one silent mutation. In contrast to the missense mutations found in PDC, it is interesting to note that the silent mutation was checked in 28T of well differentiated papillary carcinoma. These results represents molecular evidence that p53 gene aberration associated with overexpression of the mutant form of p53 protein plays a crucial role in the biologically aggressive subtypes of thyroid carcinoma, and point mutation only was not sufficient to be a prognostic marker for the biologically aggressive malignancy of thyroid tumors. There was no p53 gene aberration found in four cases of undifferentiated carcinoma (UDC) studied. The results suggest that other unknown factors should be responsible for the aggressiveness in some UDC of thyroid carcinoma except overexpression of p53.
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PMID:p53 gene mutation in thyroid carcinoma. 861 9

Neuroendocrine tumors of lung, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC) constitute a spectrum of malignancies in which the pathologist at times has difficulty in discerning tumor subtype and aggressiveness in a reproducible fashion. Therefore, 59 primary neuroendocrine lung tumors including 10 TCs, 26 ACs, 15 LCNECs, and 8 SCLCs were selected from cases collected from 1976 to 1988 and immunostained for p53 protein. All of these tumors were also genotyped for specific point mutational damage affecting p53 (exons 5, 7, and 8; with ACs additionally sequenced for p53 exon 6); 13 tumors for K-ras-2 (exon 1); and 31 tumors for c-raf-1 (exon 15) growth-regulatory genes. Genotyping was performed on topographically selected, minute tumor samples removed from unstained formalin-fixed, paraffin-embedded tissue sections (topographic genotyping) using polymerase chain reaction and direct sequencing. The distribution of p53 immunohistochemical staining had four patterns: negative in TCs, one-half of ACs, 3 of 15 LCNECs, and 1 of 8 SCLCs; less than 10% but more than five tumor cells per 10 high power fields (focal) in a subset (7 of 26) of aggressive ACs; 10 to 49% of tumor cells (patchy) in a subset (6 of 26) of ACs with a higher grade of aggressiveness; and 50 to 100% of tumor cells (diffuse), exclusively seen in LCNECs (12 of 15) and SCLCs (7 of 8). Three patterns of immunohistochemical staining intensity of p53 protein were seen: negative, weak or mild, and moderate to marked. SCLCs and LCNECs accounted for cases of moderate to marked staining and were the only ones to have mutations in p53 exons 5, 7, or 8. No mutations were found in AC and TC, showing absent to weak staining and no staining, respectively. The difference in distribution and staining intensities between LCNEC and SCLC compared with AC and TC was statistically significant (P < 0.001). Patients having AC with patchy p53 immunostaining usually had survival limited to 3 years, whereas those having AC with focal p53 immunostaining subsequently developed metastatic or recurrence of AC disease (P < 0.05). The absence of point mutations in cases with patchy or focal immunostaining suggests increased expression of wild-type p53 tumor suppressor protein likely in response to growth deregulation in a more aggressive subtype of AC. A novel hypothesis is presented in regard to these findings. K-ras-2 and c-raf-1 gene sequence analysis showed no evidence of point mutational change in any of the tumors studied. The TC and AC categories are therefore genetically distinct from the higher grade neuroendocrine SCLC and LCNEC. Immunohistochemistry for p53 on AC lung tumors may be helpful to delineate cases at higher risk for aggressive behavior. Additionally, although LCNEC is categorized as a non-small-cell carcinoma, it is more akin genetically and immunohistochemically to SCLC.
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PMID:Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. 862 22

Forty-two cases, including 21 uterine papillary serous carcinomas (UPSC) and 21 age-, nuclear-grade-, and clinical-stage-matched uterine endometrioid carcinomas (UEC), were studied immunohistochemically for p53 and bcl-2 in archival paraffin-embedded tissue. Compared to UEC (28.6% positive), UPSC (71.4% positive) had a significantly higher frequency of p53 overexpression (P = 0.005); furthermore, in a clinical-stage-matched fashion, a higher frequency of p53 overexpression was found in early-stage cases (P = 0.032), but not in late-stage cases. In a nuclear-grade-matched comparison, no statistical difference in p53 overexpression was identified between the two subtypes, although UPSC had stronger p53 immunoreactivity than UEC. Of UPSC, no difference in p53 overexpression was detected between tumors of early and late stages; additionally, in 5 cases, there was an abrupt transition from nonstaining morphologically benign glands to uniformly positive p53 nuclear staining in regions of intraepithelial carcinoma. Conversely, in UEC, there was a significant difference in p53 immunostaining between tumors of early and late stages (P = 0.01); no case had an abrupt transition for p53 immunostaining. For bcl-2 immunostaining, UEC had a significantly higher immunohistochemical staining score than did UPSC (P = 0.0002). In general, the staining intensity of bcl-2 diminished progressively from proliferative phase and hyperplastic endometrium to UEC and then to UPSC, with 3 of 21 (14.3%) UPSC being negative. These results suggest that p53 alteration may be an early event in the development of UPSC and may be related to its clinical aggressiveness, while it is a late event in UEC. Early detection of p53 nuclear accumulation may help to identify precursor lesions of UPSC. bcl-2 persistence is frequently associated with endometrial carcinoma, and failure to inactivate bcl-2 expression probably is related to the development of endometrial carcinoma.
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PMID:p53 overexpression and bcl-2 persistence in endometrial carcinoma: comparison of papillary serous and endometrioid subtypes. 862 27

The purpose of this study was to investigate a prognostic indicator that can differentiate node negative breast cancer patients (N = 39, T2N0M0) with high risk and low risk for the development of recurrence or metastases. Preoperative plasma prolactin (PRL) was estimated by radioimmunoassay. The expression of PRL, p53, nm23, and c-erbB2 was investigated by immunohistochemical (IHC) localization; cathepsin D (CD, Enzyme Linked Sorbant Assay) and estrogen- and progesterone-receptors (ER and PR, Dextran coated charcoal method) were estimated in the tumor cytosols. The follow-up period was 2-6 years. Statistical comparisons were made between each marker for relapse-free survival (RFS) and overall survival (OS). Of the 39 patients, 18 had hyperprolactinemia (PRL > 20.0 ng/ml plasma), whereas overexpression of p53 was observed in 55% (17/31) tumors. These were independently and in combination associated with a reduced RFS and OS. The rest of the investigated markers did not show promising results. Hyperprolactinemia and/or overexpression of p53 were associated with aggressiveness of the tumor, early disease relapse or metastases, and poor OS in patients with node negative breast cancer. These two markers may enhance our ability to identify node negative breast cancer patients with aggressive tumors, for whom the use of adjuvant chemo and/or endocrine therapy is unequivocally justified.
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PMID:Node negative breast carcinoma: hyperprolactinemia and/or overexpression of p53 as an independent predictor of poor prognosis compared to newer and established prognosticators. 864 46


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