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)

In order to study differences in the tumor growth and frequency of metastases between younger and older patients with lung cancer, we investigated the nuclear DNA and nuclear protein according to age by means of cytophotometry after combined staining with Feulgen and Naphthol Yellow S. On the basis of Feulgen-Naphthol Yellow S staining method, 13 patients less than 40 years old and 16 patients older than 70 years were investigated. Our results showed no significant difference in nuclear DNA contents between young and old patients, but there were significantly higher nuclear protein contents (p less than 0.05) and nuclear protein to nuclear DNA (NP/DNA) ratios (p less than 0.001) in young patients than in old patients. This suggests that young patients may have higher tumor proliferation (high nuclear protein contents and NP/DNA ratios). The lower nuclear protein content and NP/DNA ratio of older cases is in keeping with the general phenomenon of slower tumor growth and less frequent metastases in such cases.
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PMID:Quantitative cytochemical differences between young and old patients with lung cancer. 299 5

Reliable indicators of behavior in stromal tumors of the gastrointestinal tract have yet to be elucidated. Aggressive behavior has been associated with large size, hypercellularity, tumor necrosis, nuclear atypia, and high mitotic rate. Recently, new methods of measuring proliferation have been developed that exploit the phenomenon of cell cycle specific protein synthesis. In this study the expression of the S-phase specific nuclear protein proliferating cell nuclear antigen (PCNA) is tested as an indicator of malignancy. Sixteen stromal tumors of the stomach were reviewed for tumor size, cellularity, nuclear atypia, mitotic rate, necrosis, vascular invasion, and predominant cell type. Local recurrence and/or mortality were ascertained with a minimum follow-up of 5 yr. An immunohistochemical assay for PCNA was performed on a paraffin section of tumor and the percentage of positively stained cells ("PCNA index") was determined. Among the nine men and seven women, age 37 to 80 (median 66) yr, two had local recurrences that were treated surgically with no metastases. Only positive resection margin correlated with local recurrence. Two other patients developed distant metastases at 8 and 15 mo and died. Mortality did not correlate with age, sex, size, cellularity, necrosis, cell type, and vascular invasion. High grade nuclear atypia (2/2 versus 1/14, P = 0.02) and high mitotic rate (20.5 versus 5.5 per 40 hpfs, P = 0.01) did correlate with mortality. PCNA index did not correlate with local recurrence, but was sharply higher in fatal cases (6.4 versus 1.2, P = 0.001). Both fatal tumors had PCNA values above 6.0, and all others had values of 4.0 or less. The PCNA index is a proliferative marker that may have prognostic value in gastric stromal tumors.
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PMID:Stromal tumors of the stomach: prognostic value of the PCNA index. 790 52

N-myc oncogene amplification in neuroblastoma has been found to be significantly associated with advanced stage disease and tumor progression. However, there is a lack of data on tumors, regarding the relationship between N-myc gene amplification and proliferation activity. Proliferating cell nuclear antigen (PCNA) is a proliferation-induced 36 kD nuclear protein that is the auxiliary component of DNA polymerase delta. PCNA levels in tissues have been found to correlate with proliferative activity. We have examined PCNA levels in neuroblastomas in relation to N-myc gene amplification and tumor stage. Statistically, significantly higher levels of PCNA were observed in tumors with an amplified N-myc gene relative to tumors with a single gene copy. The highest levels of PCNA were observed in advanced stage tumors with an amplified N-myc gene. Treatment of neuroblastoma cells in culture with retinoic acid, which induces differentiation, resulted in a substantial decrease in PCNA. Our results suggest that PCNA levels may reflect differences in proliferative activity between neuroblastomas, related to stage of the disease and to N-myc gene copy number.
Clin Exp Metastasis 1993 Jan
PMID:PCNA levels in neuroblastoma are increased in tumors with an amplified N-myc gene and in metastatic stage tumors. 809 85

p53 is a tumor suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth. Mutations in p53 gene are the most common genetic alterations in a several human cancers, including Non Small Cell Lung Cancer (NSCLC). However, up to now, the role of p53 in the tumour's behaviour and its progression has not been completely clear. We performed immunohistochemical staining for mutated p53 using two monoclonal antibodies, PAb1801 and PAb240, in fresh tumour specimens from 103 consecutive patients who underwent surgery for resectable NSCLC. PAb1801 detects both the normal and mutant form of p53, while PAb240 is specific only for the mutant form and recognizes a denaturation-resistant epitope located between aminoacids 156-335. Both antibodies showed a mainly nuclear staining in neoplastic cells but not in surrounding uninvolved lung tissues. 68 out of 100 (68%) and 37 out of 103 (35.9%) of the cases were positive with PAb1801 and with PAb240, respectively. Tumours from patients with hilar-mediastinal lymph node involvement showed a higher p53 expression, detected by PAb1801, than those without nodal metastases (p = 0.04). Moreover, tumours expressing more than 60% of positive cells with both antibodies showed a significant increase of nodal involvement (p = 0.1; p = 0.03). Furthermore, p53 expression was significantly related to post-surgical stage (p Tumor Stage) (p = 0.04). In addition, we did not find any correlation between p53 expression and proliferating activity evaluated by PCNA, Ki-67 and DNA flow cytometric cell cycle. In conclusion, the evaluation of p53 oncogene expression may identify individuals whose resectable NSCLCs have a more aggressive tumour behaviour.
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PMID:p53 expression in non small cell lung cancer: clinical and biological correlations. 810 Apr 13

Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.
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PMID:Prognostic significance of TP53 alterations in breast carcinoma. 810 35

The aim of this study was to evaluate the power of quantitative pathology in improving the accuracy of prognosis in ductal infiltrating breast carcinoma. Ninety tumours were studied, with a diameter < or = 2.5 cm; positive (metastatic) axillary lymph nodes were found in 48 of the 90 cases; no patient had systemic metastases. Surviving patients had a mean follow-up of 106 months (minimum 69 months). At the end of the study, 45 patients were alive, 45 deceased. The histopathologic study of tumour nuclei and nucleoli included: a) geometric features, i.e., the mean and standard deviation of nuclear area, perimeter, diameter and form factor, nucleolar area and nucleolar/nuclear ratio, measured with a Kontron-IBAS automatic image analyser; b) immunohistochemical features, i.e., the percentage of PCNA (Proliferating Cell Nuclear Antigen)-positive nuclei, the expression (positive or negative) of vimentin (as a marker of tumour dedifferentiation), and the nuclear protein p53. Statistically significant differences were found between surviving and decreased patients for most features; multivariate analysis gave 92.2% accuracy in predicting outcome. Among the classes defined with multivariate analysis, it was possible to distinguish subsets of patients with bad prognosis by studying the expression of vimentin and p53, although these markers were positive in a small number of cases: 5 out of 6 patients with vimentin positivity and 4 out of 8 with p53 positivity died within 24 months of the diagnosis.
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PMID:Multivariate quantitative histopathological assessment of prognostic factors in ductal infiltrating breast carcinoma. 810 96

The proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with cells in active cell cycle. The expression of PCNA was evaluated immunohistochemically in 3-6 samples from 68 renal cell carcinomas. A total of 279 tumour samples were analysed using the monoclonal antibody PC-10, and the percentage of positively stained cell nuclei (PCNA-index) was determined. The tumour PCNA-index varied between 0.9-17.5%, with a mean value of 4.9%, significantly different from normal kidney cortex samples (p < 0.001). A significant difference in PCNA-index was found between the different tumour grades, whereas no significant difference was found between clinical stages. Concerning DNA ploidy, aneuploid tumours had a significantly higher PCNA-index compared with diploid tumours (p = 0.002). There was a significant survival advantage for patients with low tumour PCNA-indices (< 3.5%) compared with those with high indices (> 3.5%, p = 0.019), a difference also found for patients with non-metastatic disease (p = 0.012). Our data shows that PCNA expression can be analysed and that it may constitute an additional prognostic parameter for patients with renal cell carcinoma.
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PMID:Proliferating cell nuclear antigen expression in renal cell carcinoma. Prognostic implications. 900 23

Xenografts originated from human tumours offer the most appropriate research material for in vivo experimental research. However, primary human breast carcinomas are difficult to grow when transplanted in athymic mice: tumour take is less than 15%. Recently, we have achieved 60% tumour take by injecting tumour cell suspensions mixed with Matrigel. Human breast xenografts originated from primary breast carcinoma also frequently show the potential to metastasize spontaneously. In the present study, we generated a human breast carcinoma xenograft line (UISO-BCA-NMT-18) that shows 100% tumorigenicity and 80-100% lung metastasis when transplanted s.c. in athymic mice. We have studied in detail the characteristics of the xenograft and the patient's tumour from which the xenograft line originated. Both the xenograft and the patient's tumour showed intense staining for mutant p53 nuclear protein, and high expression of U-PA, PAI and u-PAR. In vivo growth of the xenograft is stimulated by exogenous supplementation of oestrogen. This xenograft is continuously growing in mice and has shown 80-100% metastasis for the last three successive in vivo passages. This well-characterized, oestrogen-responsive, metastatic breast carcinoma xenograft line will provide excellent research material for metastasis-related research.
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PMID:Development of a new metastatic human breast carcinoma xenograft line. 948 17

To determine whether the expression of transforming growth factor alpha (TGF-alpha), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-alpha, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-alpha expression was low in 42%, intermediate in 35%, and high in 23%. TGF-alpha expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-alpha expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-alpha expression in the metastasis than in the primary tumor (P = .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases (P = .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of disease-free survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-alpha expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection.
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PMID:Clinical relevance of transforming growth factor alpha, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors. 975 33

In prostate cancer, mutation of the p53 tumor suppressor gene has been associated with locally advanced disease and hormone-resistant disease that is predominantly localized to bone. However, little is known regarding the status of the p53 gene in metastatic prostate cancer that has not been treated with hormonal manipulation. We evaluated formalin-fixed, paraffin-embedded malignant tissues from 86 patients with various stages of prostate cancer, including pathologically confined, locally advanced, and metastatic disease, to detect abnormal p53 nuclear protein accumulation using immunohistochemistry. No abnormal p53 immunostaining was detected in 18 patients with prostate cancer confined to the gland. Two tumors from 21 patients with locally advanced disease (extracapsular extension and/or seminal vesicle invasion) had abnormal nuclear p53 accumulation, and a mutation in exon 7 of the p53 gene was detected in tumor DNA from one patient using single-strand conformation polymorphism-direct sequencing analysis. Of the remaining 47 patients studied in whom tissues from the prostate gland and a metastatic site (44 lymph node, 2 bone, and 1 lung) were available, only 3 had received hormonal therapy prior to obtaining metastatic tissue. In four patients both primary and metastatic tumors demonstrated accumulation of p53 protein, whereas seven additional patients exhibited p53 accumulation only at the metastatic site. In three patients the metastatic tumors harbored missense single-base substitutions in exon 5, as detected using single-strand conformation polymorphism-direct sequencing. These results indicate that p53 abnormalities are associated with lymph node metastases derived from prostate cancer patients that had not undergone hormonal therapy.
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PMID:Association of p53 mutations with metastatic prostate cancer. 981 1


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