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)

Breast cancers often contain different clones of tumor cells. Attention to the cellular properties of breast cancer metastases may identify characteristics in primary tumors that are associated with metastasis. Such characteristics could include DNA content, cell proliferation, abnormal oncogene expression, or relative cell population (clonal dominance). We examined DNA ploidy (image analysis), proliferation index (proliferating cell nuclear antigen-1 immunostaining), and expression of Her-2/neu oncoprotein in 17 invasive breast cancer samples (36 primary tumor samples) and 82 corresponding regional metastases. In all samples the primary tumor was multiclonal (usually biclonal) by DNA ploidy analysis. In approximately 90% of metastatic DNA clones (30 of 34) the corresponding clone was identified in a primary tumor sample representing 25% or more of the tumor cell population (significant clone). A majority DNA clone (> or = of tumor cell population) existed in 60% (21 of 36) of primary tumor samples and in 70% (60 of 82) of metastases (30% diploid v 70% nondiploid in both groups). In approximately 50% of metastases (37 of 82) an unexpected majority clone was identified (not a majority in any primary tumor sample) and the ratio of diploid to nondiploid clones also was 30% to 70%. However, in 80% of majority metastatic clones (46 of 60) that clone was a significant primary tumor clone. Proliferation index was quite variable in primary tumor samples and in corresponding metastases. Overexpression of Her-2/neu oncoprotein in the primary tumor of seven of 10 patients also was identified in all corresponding metastases in five of seven patients and in some metastases in two of seven patients. The metastases in three Her-2/neu-negative patients were all negative. We conclude that (1) DNA clones are stable after metastasis, (2) clonal majorities in metastases reflect clones identified in primary tumors, (3) different metastatic clones from an individual tumor can establish clonal majorities, (4) neither diploid nor aneuploid cells have a metastatic advantage in breast cancer, (5) proliferation indices are heterogeneous, and (6) overexpression of Her-2/neu is usually consistent between primary tumors and corresponding metastases.
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PMID:Breast cancer heterogeneity: evaluation of clonality in primary and metastatic lesions. 786 51

Morphometric, DNA, and proliferating cell nuclear antigen (PCNA) measurements were taken of benign melanocytic tumors and malignant melanomas. Significant differences between lesion groups according to Krushell-Wallis analysis were found in terms of mean nuclear area, coefficient of variation (cv) of nuclear area, cv of nuclear shape nuclear contour index (NCI), mean and cv of nucleolar area, DNA 2.5 c and 5 c exceeding rates, and PCNA positivity. A logistic regression analysis with respect to banal nevi versus primary malignant melanoma showed that the cv of nuclear area and the DNA 2.5 c exceeding rate were significant independent predictors. Nuclear polymorphism, i.e., the cv of nuclear shape NCI, was larger in metastasizing primary melanomas than in thin nonmetastasizing primary melanomas. PCNA positivity was occasionally increased in keratinocytes adjacent to nevi or melanomas. Larger values for nuclear area, DNA aneuploidy, and PCNA positivity were found in thick malignant melanomas and melanoma metastases than in benign melanocytic lesions and thin malignant melanomas. Morphometry, DNA content, and PCNA positivity thus seem to reflect different stages in tumor progression of malignant melanoma.
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PMID:Morphometric, DNA, and proliferating cell nuclear antigen measurements in benign melanocytic lesions and cutaneous malignant melanoma. 786 99

Mutation in the p53 tumor suppressor gene is the most common genetic alteration in human cancer. As in mutant p53 the protein is stabilised and the half-life is extended, it becomes detectable by immunohistological staining. p53 immunoreactivity thus seems to be a potential biomarker for the assessment of the oncogenic potential of malignant melanomas. In 103 tissue sections of primary and metastatic malignant melanomas of the head and neck detectable levels of p53 were only found in 3 of the primary tumors and in none of the metastases. At the same time the proliferation status of the malignant melanoma lesions was determined using the cell cycle specific antibody PCNA. 55 primary and metastatic tumors were stained with a PCNA-MAb to determine the proliferation activity of the tumors. The results of our immunohistochemical investigation suggest that immunoreactivity of p53 cannot be used to determine the malignant potential of melanomas in the head and neck. PCNA staining showed that the majority of the tumors and metastases were proliferating rapidly.
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PMID:p53 and PCNA expression in malignant melanomas of the head and neck. 788 8

K-ras mutations in colorectal tumors (53 carcinomas, 21 adenomas) were investigated using oligonucleotide probes specific for mutations at codon 12, 13, or 61 of the K-ras gene by polymerase chain reaction and oligonucleotide hybridization techniques, and the proliferative activities were assessed immunohistochemically by using anti-proliferating cell nuclear antigen (PCNA), counting PCNA labeling index (LI). Point mutations were observed 18.8% in the adenomas, 40.0% in the intramucosal carcinomas and 27.0% in the invasive carcinomas. Fewer incidences of K-ras mutations in the invasive carcinoma suggested carcinomas without K-ras mutation invade rapidly. Clinicopathologically, K-ras mutation-positive carcinomas tended to show the presence of venous invasion (p < 0.005). There were many distant metastases in the K-ras mutation-positive cases (p = 0.07). Moreover, among adenocarcinomas a significant correlation was demonstrated between PCNA LI and the pattern of infiltrating growth (p < 0.05). Our data imply that the K-ras mutation gains access to invasion and metastasis, as well as the ras mutation occurs at the initiation of the carcinoma. The present data suggest that K-ras mutations in colorectal carcinomas are correlated with venous invasion, while cell proliferative activities are related to stromal invasion, and these factors are independent markers for invasion of colorectal carcinomas.
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PMID:[Cell kinetics of colorectal tumors with assessment by K-ras mutation and PCNA labeling index]. 790 93

Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitates the assessment of proliferation in routinely fixed, paraffin-embedded tissue sections. In this study we investigated the expression of PCNA in 29 Spitz's naevi in comparison with 43 primary malignant melanomas (MM), 18 cutaneous metastases of malignant melanoma (MMM) and 16 benign melanocytic naevi (BMN). After selection of the microscopic field with the highest number of PCNA-positive nuclei, the nuclear density (NDmax) of PCNA-stained nuclei in this field was assessed using interactive image analysis. The mean value of NDmax (given as 1000 nuclei/mm3 tissue) of SN was 27.9 (+/- 16.7) and differed significantly from that of MM (48.1 +/- 40.5; U-test: p < 0.05) and that of MMM (114.4 +/- 56.3; p < 0.01). Comparing NDmax of the subgroups of MM according to their maximal vertical tumour thickness with NDmax of SN we found significant differences only between SN and MM > 1.5 mm thick (n = 14; NDmax = 67.8 +/- 36.1) but not between SN and MM < or = 1.5 mm thick (n = 29; NDmax = 38.8 +/- 39.3). PCNA expression in SN did not differ from that of BMN (NDmax 23.8 +/- 28.5). Proliferative activity as assessed by measurement of PCNA expression therefore showed significant differences between BMN, SN and thin primary melanomas on one hand and thick primary melanomas and cutaneous metastases of malignant melanomas on the other hand.
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PMID:Proliferative activity in Spitz's naevi compared with other melanocytic skin lesions. 790 41

Alcohol- and formalin-fixed, paraffin-embedded samples of 71 brain tumors (35 gliomas, 22 metastatic carcinomas, 8 meningiomas and 6 other tumors) were investigated by immunocytochemistry with three different monoclonal antibodies against proliferating cell nuclear antigen (PCNA)/cyclin (19A2; 19F4; PC10). PC10 was found to work best; it is applicable to both alcohol- and formalin-fixed tumor samples. PCNA labeling indices (LIs) were compared in the same tumors with LIs obtained by Ki-67 immunostaining of frozen sections and by in vitro incubation with bromodeoxyuridine (BrdUrd); in the latter preparations, BrdUrd LIs could be compared with PCNA LIs in the very same areas of serial sections. In gliomas, PCNA LIs were 0.7-80.2% (mean 31.7%), in metastases 0-76.0% (mean 47.8%), and in meningiomas 0-53.0% (mean 19.3%). In general, PCNA LIs were highly significantly correlated with Ki-67 LIs (P = 0.0002) and BrdUrd LIs (P = 0.0001). However, when tumor subgroups are considered, only gliomas show a significant correlation with Ki-67 and BrdUrd LIs. Despite this statistical correlation, PCNA expression was out of proportion to proliferation indices as determined by both other methods in almost one third of all brain tumors. Immunocytochemistry for PCNA produces a broad spectrum of staining intensity of labeled nuclei, whose number is dependent upon the sensitivity of the immunocytochemical technique used. Thus, inter-observer and inter-laboratory variabilities in PCNA LI determination may occur. Overlapping of PCNA LIs between tumor subgroups of varying malignancy further limits the informational value for the individual case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunostaining for proliferating cell nuclear antigen: its role in determination of proliferation in routinely processed human brain tumor specimens. 790 72

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

Expression of four biologic markers was studied in 69 cases of endometrial cancer to identify their association with cell type, decreased survival, and increased tumor metastasis. Cell types included endometrioid (n = 45), serous papillary (n = 16), and clear cell (n = 8). Immunohistochemical stains were employed to detect the presence of epidermal growth factor receptor (EGFR), HER-2/neu, p53, and proliferating cell nuclear antigen (PCNA). Analysis revealed that EGFR was expressed in 49%, HER-2/neu in 59%, p53 in 9%, and PCNA in 16% of tumor specimens. HER-2/neu overexpression was significantly associated with depth of myometrial invasion. p53 and PCNA immunoreactivity significantly correlated with nonendometrioid histology, although PCNA was less specific in labeling these less favorable cell types. EGFR immunoreactivity also significantly correlated with nonendometrioid cell types and tumor metastases at time of diagnosis. Seventy-seven percent of patients with metastatic disease were EGFR-positive versus 36% positivity in patients with no evidence of metastases (P < 0.002). For patients with endometrioid adenocarcinoma, evidence of EGFR overexpression decreased survival from 89 to 69% (P < 0.04). In the serous papillary and clear cell category, EGFR positivity decreased survival from 86 to 27% (P < 0.03). EGFR strongly correlates with tumor metastasis and patient survival in endometrial cancer. Altered expression of this oncoprotein may serve as a guide to prognosis and treatment in these patients.
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PMID:Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. 790 88

The expression of the proliferating cell nuclear antigen (PCNA) was analyzed in formalin-fixed paraffin-embedded materials of 20 primary renal pelvic and ureteral cancers. The relation between PCNA positive rate and clinical pathological stage and prognosis were investigated. The fraction of PCNA positive nuclei ranged between 1.6-64.4% (mean 25.1%). The PCNA positive rate was found to be related to established prognostic factors, but not to patient age, sex and length of time for paraffin-embedded. Grade 3 cancers showed a higher fraction of PCNA positive nuclei than grade 1 and 2 cancers (p < 0.05). Superficial cancers showed a significantly lower fraction on nuclei positive for PCNA than invasive cancers (p < 0.01). The cancers with lymph node metastases showed a higher fraction (p < 0.05). The cancers with distant metastases postoperatively, also had a higher fraction (p < 0.05). As PCNA immunostaining can be applied to routinely processed paraffin-embedded specimen, this method is very useful to assess the cell proliferation. The results suggest that the fraction of PCNA positive nuclei would be useful for investigating the malignant potential, of renal pelvic and ureteral cancers thereby providing prognostic factors of these diseases.
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PMID:[The expression of proliferating cell nuclear antigen (PCNA) immunostaining in renal pelvic and ureteral cancers and its prognostic value]. 791 44

A positive correlation between PCNA and the most important histoprognostic factors of cutaneous melanoma has been demonstrated. The aim of our work was to evaluate the efficacy of PCNA in predicting melanoma recurrence and to compare it with that of Breslow thickness. One-hundred and fifteen patients (75 women, 40 men; mean age 50 years) with primary cutaneous melanoma were retrieved. pTNM stages were as follows: stage I, 54 patients; stage II, 31 patients; stage III, 26 patients; and stage IV, four patients. The mean follow-up period was 55 months (range 2-260). Six patients developed lymph node metastases and 28 developed distant metastases; 27 patients died within 2-202 months from diagnosis. Tumour thickness was re-evaluated for each case. PCNA immunostaining was performed using the avidin-biotin complex method and the percentage of PCNA-positive tumour cells was indicated as the PCNA index. In order to evaluate and compare the PCNA index and Breslow thickness as predictors of recurrence, the receiver-operating characteristic (ROC) curve method, based on true-positive and false-positive rates was used. The PCNA index showed the highest true-positive rates and the lowest false-positive rates in the 5-30 interval. The PCNA index optimal cut-off is 20, characterized by 70% sensitivity and 80% specificity; Breslow thickness optimal cut-off is 3.5 mm, with 40% sensitivity and 90% specificity. Our results indicate that the PCNA index has a higher efficacy in predicting locoregional and distant recurrences in patients presenting primary cutaneous melanoma.
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PMID:Proliferating cell nuclear antigen (PCNA) and recurrence in patients with cutaneous melanoma. 795 Mar 56


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