Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumor suppressor gene has recently been implicated in the pathogenesis of human esophageal cancer. To assess potential clinical applications for this molecular marker, 52 patients with primary esophageal adenocarcinoma were studied prospectively. p53 protein accumulation was evaluated immunohistochemically in surgically resected esophageal tissues, and correlated with clinicopathologic findings and survival. All patients underwent total esophagectomy with reconstruction, completely resecting all gross disease. Immunopositivity was seen in 28 of 52 (54%) primary adenocarcinomas, and was associated with a trend towards reduced postoperative survival (P = 0.06; log-rank). Regional lymph node metastases were found in 30 (58%) patients. Thirteen of 30 (43%) regional lymph node metastases were immunopositive, which was the most significant predictor of overall survival by univariate (P = 0.02; log-rank) and multivariate analysis (P = 0.05; Cox regression). This study further implicates p53 in esophageal tumor development and progression. The immunohistochemical finding of p53 protein in primary esophageal adenocarcinomas and regional lymph node metastases appears to be associated with reduced overall survival for this disease. If these preliminary observations are confirmed in larger prospective studies, p53 may prove to be a clinically useful molecular marker in future clinical trials of esophageal cancer.
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PMID:Prognostic value of p53 protein in esophageal adenocarcinoma. 766 67

In the present study, we investigated the expression of the tumour suppressor protein p53 in 113 primary and 43 metastatic malignant melanomas by immunohistochemistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome. In primary melanomas, the polyclonal anti-p53 antibody CM-1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over-expression was detected. Immunohistochemistry, using the monoclonal antibody DO-1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immunoreactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P < 0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P < 0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (< 1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow-up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over-expression was detected by CM-1. However, this difference was not statistically significant. The results of the present study indicate that immunoreactivity to anti-p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of p53 protein in malignant melanoma: clinicopathological and prognostic implications. 766 36

Identification of the genetic alterations that occur in tumors is an important approach to understanding tumorigenesis. We have used comparative genomic hybridization (CGH), a novel molecular cytogenetic method, to identify the gross DNA copy number changes that commonly occur in small cell lung cancer (SCLC). We analyzed ten SCLC tumors (seven primary tumors and three metastases) from eight patients. We found frequent increases in DNA copy number on chromosome arms 5p, 8q, 3q, and Xq and frequent decreases in copy number on chromosome arms 3p, 17p, 5q, 8p, 13q, and 4p. The increase in copy number at 8q24 (MYC) and decreases at 17p13 (TP53), 13q14 (RB), and 3p have previously been identified in SCLC with other methods. Many of the other regions in which we detected common copy number changes have not been reported to be regions of common alteration in SCLC tumors. Comparison of copy number changes between a primary tumor and a metastasis from the same patient showed that they were more closely related to each other than to any of the other tumors. The results of direct CGH analysis of SCLC tumors reported here confirm the existence of copy number changes that we identified previously by using cell lines.
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PMID:Identification of novel regions of altered DNA copy number in small cell lung tumors. 766 37

p53 is a tumor suppressor protein that is overexpressed in a variety of human neoplasms, including prostatic adenocarcinoma. Recent studies have demonstrated a significant positive correlation between extent of p53 overexpression and tumor grade in prostatic adenocarcinoma. Because it appears that mutations of p53 might play a role in the pathogenesis of a subset of biologically aggressive prostatic neoplasms, we sought to examine the frequency of p53 overexpression in primary and metastatic prostatic adenocarcinoma. Using a monoclonal antibody (D07) directed against both the wild-type and mutant forms of p53, we examined p53 immunoreactivity in 36 cases of primary prostatic adenocarcinoma, 17 cases of metastatic prostatic adenocarcinoma involving lymph nodes and 15 cases of metastatic prostatic adenocarcinoma involving bone. Twenty-eight percent (10/36) of the primary tumors displayed nuclear staining for p53. Increased p53 immunoreactivity was observed in only 6% (1/16) of prostatic adenocarcinomas with a total Gleason score of 6 or less, as compared with 45% (9/20) of those adenocarcinomas with a Gleason score of 7 or more. Fifty-nine percent (10/17) of the lymph node metastases and 43% (6/14) of the bone metastases displayed nuclear immunoreactivity for p53. Our results indicate that increased p53 expression is positively correlated with increased histologic grade and with the presence of metastatic disease in patients with prostatic adenocarcinoma, and they suggest that mutations of the p53 gene may play a role in mediating the behavior of a biologically aggressive subset of this common neoplasm.
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PMID:p53 immunoreactivity in primary and metastatic prostatic adenocarcinoma. 767 61

Preoperative staging of gastric cancer plays a crucial role every multimodal treatment protocol. At present, staging intends to be far more than evaluation of the depth of tumor infiltration into the organ wall, that is, T stage, nodular status (N category), and the presence of distant metastases (M stage) according to UICC criteria. In modern surgical oncology it includes more often the evaluation of prognostic factors such as the RAS-protein, p53 tumor suppressor gene, growth factor receptors, cell adhesion molecules, proteolytic factors, and proliferation-associated antigens. Furthermore, evaluation of nodular status is possible by sophisticated computer programs. The conventional staging of gastric cancer using endoscopy and sonography, conventional ultrasonography, computed tomography, and magnetic resonance imaging is discussed. Possible improvements of staging in oncologic centers should include surgical laparoscopy, laparoscopic ultrasonography, and meticulous evaluation of an abdominal lavage including immunohistochemical detection of free tumor cells. The most promising tumor biology-related prognostic factors in gastric cancer are briefly discussed.
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PMID:Preoperative staging of gastric cancer as precondition for multimodal treatment. 767 91

Using monoclonal antibody PAb 1801, p53 protein was detected in the neoplastic cells of 39 (46.9%) of 83 colorectal carcinomas studied. Patients with p53+ tumors showed a higher incidence of lymph node and liver metastases (p = 0.035); in patients whose tumors were located in the rectosigmoid, p53 expression also correlated with a more advanced stage according to Dukes' classification (p = 0.015) as well as nodal (p = 0.006) and liver (p = 0.019) metastases. Following amplification of exons 5 to 8 of the p53 gene by means of the polymerase chain reaction technique, single-strand conformation polymorphism analysis disclosed an anomalous migration pattern in 23 of the 39 p53+ tumors and in four of the 35 p53- tumors analyzed. Sequence analysis showed G:C-->A:T transitions in 63.6%, G:C-->T:A and G:C-->C:G transversions in 18.2%, deletions and insertions in 13.6%, and A:T-->G:C transitions in 4.6% of the cases. Loss of heterozygosity was studied in the DNA of 79 patients; allelic loss was found in 29 (49.1%) of the 59 informative patients. Loss of heterozygosity was correlated with p53 overexpression (p = 0.0002) as well as with the presence of mutations as detected by single strand conformation polymorphism analysis (p = 0.0024).
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PMID:Association of p53 gene and protein alterations with metastases in colorectal cancer. 769 48

We have analysed 78 head and neck carcinomas (50 node metastases and 28 primary tumors including 13 matched specimens) in 65 patients for p53 alterations. Mutations were found in 54 (69%) tumors. Of the 53 mutations within exons, 40 (76%) were missense, five (9%) nonsense and eight (15%) microdeletions or microinsertions. Twenty-five (47%) mutations were transitions mostly G-->A (40%) and 20 (38%) were transversions, mostly G-->T (25%), thus confirming the role of tobacco carcinogens in the induction of these mutations. The incidence of mutations was not different in primary tumors (68%) and node metastases (70%) indicating that this gene alteration was not related to the metastatic dissemination. For eight patients, mutations were observed in matched primary tumors and metastases, indicating clonal dissemination of tumor cells in most of these carcinomas. There was a good correlation between mutations and protein overexpression (Fisher's exact test P < 10(-4). Immunostaining was also observed in basal cells from normal epithelium and in early lesions adjacent to the primary tumor in 11/15 (73%) specimens irrespective of the presence of mutation in the corresponding tumors. These data confirm that p53 overexpression is an early event in the multistep process of epithelial cell carcinogenesis. Loss of heterozygosity for the TP53 locus was detected in 54% of tumors but no association was found with mutation (Fisher's exact test P = 0.14). No mdm-2 amplification was detected in any tumors. No correlation was found between mutation and clinical parameters, the 5-year survival rates were not different (log rank test P = 0.39) in patients with and without mutation. In conclusion, we have shown that p53 gene mutations and deletions and protein overexpression are frequent in the most aggressive head and neck carcinomas but are not associated with disease progression. The presence of protein in normal mucosa and in non-invasive lesions may constitute a biomarker for early stages of carcinogenesis.
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PMID:High incidence of p53 alterations (mutation, deletion, overexpression) in head and neck primary tumors and metastases; absence of correlation with clinical outcome. Frequent protein overexpression in normal epithelium and in early non-invasive lesions. 770 Jun 47

The occurrence of mutations within the coding sequence of the p53 tumour suppressor gene is now well documented for squamous cell carcinomas of the head and neck region. However, evidence that these mutations are required for the maintenance and progression of squamous tumours is still formally lacking. To test this we have examined whether p53 mutations detected in primary squamous cell carcinomas of the tongue are also detected in the corresponding lymph node metastases. Three different p53 mutations were detected in each of three primary tongue squamous cell carcinomas (SCC), and in each case the same mutation was detected in a lymph node metastasis excised from the same patient. Although the sample number is small, the chance of obtaining the same p53 mutation independently in both the primary and metastatic tumour of each patient is at least 10(-4), therefore the results indicate that keratinocytes harbouring these p53 mutations possess a selective advantage throughout SCC progression.
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PMID:Maintenance of identical p53 mutations throughout progression of squamous cell carcinomas of the tongue. 770 3

Mutational changes in the p53 tumor suppressor gene are the most frequent genetic alterations in human malignant tumors. Studies have shown a correlation of p53 expression in breast cancer with tumor prognosis. In contrast to mutational activation of ras and GSP in thyroid tumors, little is known about the role of p53 in thyroid tumor development. Therefore thyroid tumors and thyroid tumor cell lines were studied for the presence of p53 mutations. Snap-frozen tissues from 57 differentiated thyroid carcinomas (DTCs) and 5 goiters were studied by immunohistochemical methods. A panel of six antibodies (pAb 240, 421, 1620, 1801, DO7, and CM1) was employed by using the ABC technique. Five cell lines from DTCs (FTC133, 236, 238, PTC337, MTC164) were examined by the same technique. Additionally, genomic DNA from the cells was amplified by the polymerase chain reaction (PCR) and the PCR product studied for p53 mutations (R273H) by mutation-specific oligonucleotide hybridization (MOH) and temperature gradient gel electrophoresis (TGGE) for the p53 exon 8. None of the benign thyroid tumors and 7 of 57 (12%) DTCs strongly express p53 with a heterogeneous distribution in the tumor tissue. All seven patients have metastatic disease or dedifferentiated tumors G3 (three of seven). CM1 was positive in two cell lines (FTC-133, PTC-337), questionable in FTC-238, and negative in FTC-236 and MTC-164. All three follicular cell lines, however, and the original tumor tissue showed the same p53 mutation (R273H) in MOH analysis and TGGE. P53 mutations are rare in thyroid tumors, but the presence of p53 mutations indicates a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of P53 in human thyroid tumors. 772 41

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.
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PMID:Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. 773 90


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