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)

Thirty-nine mammographically detected, (M-detected) small invasive carcinomas of the breast (< or = 5 mm) were compared with 78 consecutive clinical cancers (> or = 10 mm) for a variety of morphological and biological markers of prognostic importance. There were more tubular carcinomas in the M-detected group (12.8% v 3.8%), but this did not reach statistical significance. Incidences of other histological types were similar. The types of associated in situ component were similar in the two groups. M-detected cancers were of lower overall grade (P < .001), lower architectural and nuclear grades (P = .0164 and P < .0001 respectively), and had fewer mitotic cells (P < .0001). None showed positive lymph nodes (P < .0001). Estrogen and progesterone receptor expression was similar in both groups. M-detected cancers expressed p53 nuclear protein less frequently than clinical cancers (P = .0398), had lower levels of microvessel density (P = .0001), and were more often diploid (P = .0131). S-phase of diploid tumors in the two groups was similar, but S-phase of aneuploid tumors was lower in the M-detected group (P = .0057). Ki67 expression was lower in M-detected cancers (P < .0001). In conclusion, M-detected small breast cancers, although invasive, represent an evolutionary phase of breast cancer that generally lacks morphological and biologic markers of aggressive behavior. The presence or absence of these markers, collectively, may explain the influence of tumor size on survival in patients with breast cancer.
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PMID:Morphological and biological characteristics of mammogram-detected invasive breast cancer. 881 90

In this retrospective study we have investigated the expression of Ki-67 and p53 in 175 random cases of cutaneous squamous cell carcinomas by using the monoclonal antibodies MIB-1 and DO-1, respectively. The expression of these antibodies was compared with various histological parameters of prognostic significance. The staining results were also compared with the clinical outcome of the patients. MIB-1 and DO-1 staining showed statistically significant correlation with histopathological grade of the tumor (p < 0.0001 and p = 0.0016, respectively). The degree of immunolabelling of these antibodies also showed significant correlation with tumor depth and tumor thickness (MIB-1 thickness p = 0.02 and depth p = 0.026, and DO-1 thickness p = 0.014 and depth p = 0.005). The majority of the squamous cell carcinomas in our series were Clark's level IV, which therefore did not correlate with the extent of immunoreactivity (MIB-1, p = 0.098; and DO-1, p = 0.885). Mean length of clinical follow-up was 5.2 years. Aggressive tumor behaviour was seen in 17 patients (10.6%) with 6.9% and 3.4% local recurrences and nodal metastasis respectively. A total of 89.4% patients remained disease-free following their definitive surgical treatment. Vulval skin represented the commonest site associated with unfavourable clinical outcome (five of 17 cases). A large number of squamous cell carcinomas in this poor prognosis group showed a high prevalence of immunoreactivity of the antibodies but this did not achieve any statistical significance. We conclude that Ki-67 and p53 expression in cutaneous squamous carcinoma is not an independent predictor of prognosis.
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PMID:Prognostic significance of Ki-67 and p53 immunoreactivity in cutaneous squamous cell carcinomas. 887 97

Cystic tumors of the pancreas form a heterogeneous group, with benign, premalignant, and malignant tumors. The molecular events that underlie their neoplastic transformation process are poorly understood. Our purpose was to study DNA ploidy by flow cytometry and p53 protein expression by immunohistochemistry in a large series of cystic tumors of the pancreas. The series of 51 surgical specimens included 18 serous cystadenomas, 20 mucinous cystic tumors (benign, n = 14; borderline, n = 1; malignant, n = 5), 10 intraductal papillary-mucinous tumors (benign, n = 4; borderline, n = 1; malignant, n = 5), and 3 papillary and cystic tumors. The p53 protein immunohistochemical study was done in all cases on deparaffinized sections stained with the monoclonal antibody DO7. DNA flow cytometry was performed in 31 cases on formalin-fixed and paraffinembedded material. Neither p53 protein immunoreactivity nor DNA aneuploidy was observed in any case of serous cystadenoma. p53 protein overexpression was present in four of five malignant mucinous cystic tumors but was absent in benign and borderline cases. Only one case of malignant mucinous cystic tumor was DNA aneuploid. All benign and borderline intraductal papillary-mucinous tumors were p53 negative, and two of five malignant cases were p53 positive. There was no DNA aneuploidy in any case of intraductal papillary-mucinous tumors. The three cases of papillary-cystic tumors showed neither p53 protein immunoreactivity nor DNA aneuploidy. In cystic tumors of the pancreas, p53 protein overexpression and DNA aneuploidy are rare events, restricted to malignant cases, mostly mucinous cystadenocarcinomas. Our results confirm that this group of tumors is heterogeneous and underline the need for earlier markers of an aggressive behavior.
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PMID:p53 protein expression and DNA ploidy in cystic tumors of the pancreas. 888 45

Thirty-four uterine serous carcinomas, a type of endometrial carcinoma with aggressive behavior and a high frequency (90%) of p53 gene mutations, were analyzed for microsatellite instability (MI). Genomic DNA isolated from paired normal and tumor tissue was analyzed at eight microsatellite loci (D2S119, D2S123, D2S147, D10S197, D13S175, D18S58, D18S69, and ATn) located on four different chromosomes. All 34 tumors failed to meet the criteria for MI, defined as an alteration in the size of at least two of the microsatellite loci in tumor DNA when compared with normal DNA. Only three tumors demonstrated a shift in the size of a single microsatellite locus. Previously we reported MI in 20% of uterine endometrioid carcinomas, the most common type of endometrial carcinoma. The observed difference in the MI frequency between endometrioid and serous carcinoma is statistically significant (P = 0.003). Our data demonstrate that MI is uncommon in uterine serous carcinoma and support that different pathogenetic mechanisms are involved in the development of the two most common types of endometrial carcinoma.
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PMID:Microsatellite instability is uncommon in uterine serous carcinoma. 900 24

Assessment of the malignant potential of parathyroid tumors in the absence of metastasis can be difficult using morphologic criteria alone. The role of prognostic markers that may assist in evaluating aggressive behavior in these tumors has not been fully studied. We performed a retrospective study of 31 parathyroid lesions, including 10 adenomas, 10 atypical lesions, and 11 carcinomas, to evaluate the diagnostic and prognostic role of the MiB-1, p53, RB, and bcl-2 markers by immunohistochemical techniques. The mean tumor proliferative fraction (TPF), expressed as the number of MiB-1-positive nuclei per 1000 cells, was 20.3 in adenomas (range, 5-51), 20.0 in atypical lesions (range, 8-36), and 79.8 in carcinomas (range, 4-133). Only 1 of 20 benign lesions had a TPF more than 40, and only 2 of 11 carcinomas had a TPF less than 40. One atypical lesion and two carcinomas showed scattered cells positive for p53. Patients with the adenoma with increased TPF and the atypical lesion with positive p53 have been free of disease for 16 months. bcl-2 was expressed in 7 (70%) of 10 adenomas, 2 (20%) of 10 atypical lesions, and 4 (36%) of 11 carcinomas. Two of the 11 carcinomas were RB negative, whereas all of the 20 benign lesions were RB positive. We conclude that high TPF (greater than 40 as measured by staining with MiB-1) strongly correlates with malignancy and, therefore, may be useful in the diagnosis of carcinomas. Negative RB stain, although not a common event, may be helpful to exclude benign lesions. Other tumor markers (p53 and bcl-2) were not useful in distinguishing malignant from benign lesions.
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PMID:The role of prognostic markers (MiB-1, RB, and bcl-2) in the diagnosis of parathyroid tumors. 902 22

Merkel cell carcinoma is a very rare tumor. This is why it is not known whether this neoplasm behaves differently in the vulvar location than at other sites. We present a patient with a Merkel cell carcinoma assessed with a light optical microscope, immunohistochemistry, and electron microscope. Only eight previous cases have been reported in the literature. We discuss pathologic findings, such as histologic trabecular pattern under the optical microscope and neurosecretory granules (similar to Merkel cell carcinoma of the skin) under the electron microscope. Also discussed are the results of immunohistochemistry for low-molecular-weight cytokeratin, neuron-specific enolase, chromogranin, and Leu 7, and molecular study of N-ras, K-ras, N-myc, and p53 genes. Little is known about Merkel cell carcinoma of the vulva, but it seems to have a more aggressive behavior and poorer prognosis than Merkel cell carcinoma at other sites.
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PMID:Merkel cell carcinoma of the vulva. 906 65

The mammalian cell cycle is controlled by regulators of the G1 to S transition such as tumor suppressor proteins, p53 and retinoblastoma (RB); cyclin D1 and cyclin-dependent kinase 4; and inhibitor of cyclin dependent kinase, p16INK4A. Recently, aberrations of these cell cycle-related genes have been reported to contribute to the formation and development of cancer. In human hepatocellular carcinoma (HCC), high frequencies of aberration have been detected in the p53 and RB genes. Loss of heterozygosity (LOH) of chromosome 13q was detected in 35% of HCC and LOH on chromosome 17p was detected in 49%. Mutation of the p53 gene was also detected in 32%. The aberrations of these genes were observed more frequently in poorly differentiated and in advanced HCCs. On the other hand, genetic alterations of the cyclin D1 and p16INK4A genes were not so frequent, but appeared to be associated with the aggressive behavior of the tumor, which suggests that disruption of the cell cycle-related genes results in the progression of HCC. Further study with a substantial number of cases is required to determine the actual frequency of the aberrations of the G1 controlling genes in hepatocarcinogenesis.
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PMID:Alteration of cell cycle-related genes in hepatocarcinogenesis. 930 64

Evolving trends in the management of rectal cancer have focused on organ preservation, improved quality of life, and survival of patients. A significant shift is underway in our thinking about what constitutes the true rectum and defining the "proximal" and "distal" segments of the rectum. Tumor mobility remains a dominant prognostic factor in patient selection and choice of surgery. A clinical staging with tumor location in the rectum provides a logical algorithm for treatment decision making with either chemoradiation therapy or surgery as initial treatment of choice. Current rectal cancer management has largely focused on postoperative adjuvant radiation strategies with improvement reported for T3 and N+ cases. Recent data from Europe suggests that preoperative radiation has a significant advantage over surgery alone or postoperative treatment. This appears to be borne out by institutional studies of high-dose preoperative radiation (>45 Gy) in the United States. Aggressive preoperative combined chemoradiation has also led to significant downstaging of cancer with pathological complete response rates of 20% to 30%. This offers new options for surgical management of residual disease with endocavitary radiation or local excision. The development of new agents Gemcitabine, paclitaxel, and CPT-11 may also prove beneficial. New treatment strategies need to be coordinated with evolving knowledge of the biological behavior of the tumor based on its genetic fingerprints. c-Ki-ras and C-myc mutations have been implicated in tumor initiation and progression. A number of other tumor suppressor genes, APC gene, p53, and DCC have also been implicated in colorectal tumor carcigenesis. The modification of biological behavior by mutations in these genes is currently under study. This may guide new treatment strategies significantly reducing the death rates from rectal cancer and improving functional results of treatment.
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PMID:Critical issues in the evolving management of rectal cancer. 942 68

Clinicopathological, immunohistochemical and molecular genetic analyses of endometrial carcinoma suggest different pathogenetic pathways for endometrioid and serous carcinoma. Most endometrioid carcinomas are associated with endometrial hyperplasia, are ER/PR positive, p53 negative and express low Ki-67. In contrast, almost all serous carcinomas develop from endometrial intraepithelial carcinoma (EIC) in a background of atrophy. These tumors are ER/PR negative, strongly express p53 and show high Ki-67 labeling. On the molecular genetic level, 25-30% of endometrioid carcinomas show microsatellite instability (MI), 25-30% harbor mutant K-ras and less than 10% have mutant p53. In contrast, more than 90% of serous carcinomas have p53 mutations, 2% K-ras mutations and none MI. Among endometrioid carcinomas, K-ras mutations occur most frequently in FIGO grade 2 and 3 tumors and p53 mutations in FIGO grade 3 tumors. In contrast, MI is equally distributed among all FIGO grades. These findings support the view that endometrioid carcinoma develops slowly in a progressive fashion from endometrial hyperplasia. Mutation of p53 occurs late in tumor progression. Thus, endometrioid carcinogenesis resembles the proposed model for colorectal carcinogenesis. In contrast, serous carcinoma develops rapidly from EIC in a background of atrophy. Mutation of p53 occurs early in serous carcinogenesis and this may account for the highly aggressive behavior of this tumor.
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PMID:A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. 947 74

The cyclin-dependent kinase inhibitor p27 is a negative regulator of the cell cycle and a potential tumor suppressor gene. Because we had previously demonstrated that loss of p27 protein is associated with aggressive behavior in colorectal adenocarcinomas, we used immunohistochemistry and in situ hybridization to evaluate the potential role of alterations in p27 expression in primary and metastatic colorectal adenocarcinomas. Parallel immunostaining was performed for Ki-67 and p53. We evaluated 13 cases of metachronous and 23 cases of synchronous primary and metastatic colorectal tumor pairs. In the synchronous subgroup (Stage IV tumors), 57% of the primary tumor and metastases pairs did not express p27 protein and the remainder were low expressors. In the metachronous subgroup, 54% of the primary tumors were low expressors and the remainder high expressors of p27 protein. There was a significant reduction in the expression of p27 in the metachronous metastases (mean positive cells: 14.5%) when compared to the corresponding primary tumors (mean positive cells: 41.8%), P = 0.0023. All the primary and metastatic tumors in the metachronous subgroup showed high levels of p27 mRNA expression. There was no association between loss of p27 and either Ki-67 count or p53 expression. Because p27 is known to be up-regulated when epithelial cells are grown in suspension, the down-regulation of p27 in circulating tumor cells may confer the ability to grow in an environment of altered extracellular matrix or intercellular adhesion properties, two situations which may facilitate metastases.
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PMID:Down-regulation of p27 is associated with development of colorectal adenocarcinoma metastases. 973 17


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