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)

Gastrointestinal stromal tumors (GISTs), as currently defined, are mesenchymal tumors of the gastrointestinal tract composed of spindled and/or epithelioid stromal cells that are neither mature Schwann cells nor smooth muscle cells. Many studies have lumped GISTs from all gut sites, when in fact these tumors differ histologically by location. In this study, we evaluated a set of parameters by both univariate and multivariate analysis to determine which parameters correlated with metastases in 36 GISTs from the jejunum and ileum, exclusively. The parameters included organoid architecture, cellularity, mitotic counts, epithelioid cell shape, mucosal invasion, tumor size, skeinoid fibers, nuclear pleomorphism, ischemic necrosis, immunohistochemical differentiation, and proliferating cell nuclear antigen labeling. We evaluated these retrospectively without knowledge as to the metastatic outcome of the tumors. By univariate analysis, dense cellularity, mitotic counts, epithelioid cell shape, mucosal invasion, and size were statistically significant correlates with metastases. By multivariate analysis, only dense cellularity and mitotic counts were independent correlates with metastases. Whether these features are useful predictors of behavior remains to be tested.
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PMID:Stromal tumors of the jejunum and ileum. 907 27

Our purpose was to study the role of the expression of P-glycoprotein (Pgp) and glutathione S transferase-pi (GST-pi) in predicting the response to chemotherapy, relapse-free interval, and survival of patients with synovial sarcoma (SS). Thirty-seven cases of primary SS, without regional lymph node or distant metastases, were studied. There were 17 females and 20 males, ranging in age from 7 to 81 years (median, 31 years) with tumors located in the lower extremity (n = 24) upper extremity (n = 5) and trunchus (n = 8). The cases were retrospectively studied without knowledge of clinical course to compare the immunohistochemical expression of Pgp and GST-pi, flow cytometry parameters (ploidy and % of cells in S+G2 phases), and PCNA and Ki-67 labeling of primary tumors before any therapy, with that observed in local recurrences and metastases after chemotherapy. The relationship of the aforementioned parameters with clinicopathological features (gender, age, and histo-blood group of the patients, size, location, histological subtype. TNM stage, and clinical response to chemotherapy of the tumors) was also evaluated. Results revealed that Pgp and GST-pi were expressed in 29.7% and 40.5% of the cases, respectively. In 48.6% of the tumors there was expression of a least one of the drug resistance markers. The markers were coexpressed in 25.0% of the tumors. The prevalence of Pgp expression was lower, but not significantly, in stage I-II (17.6%) than in stage III (40.0%) tumors, and also in cases without clinical progression (16.7%), than in cases with (36.0%). No such differences were observed for GST-pi expression. Pgp and GST-pi expressions were significantly associated with biphasic SS and were particularly noticeable in solid/glandular areas of biphasic SS. The expression of the drug resistance markers was not significantly associated with gender, age, and histo-blood group of the patients, dimension, location, and proliferative activity of the tumors; it was also not significantly related to relapse-free interval and survival of the patients. The expression of Pgp and GST-pi was not significantly associated either to response to chemotherapy or influenced by chemotherapy. We conclude that Pgp and GST-pi expressions are not good predictors response to of the chemotherapy in patients with localized SS. Other drug resistance mechanisms may be active in SS.
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PMID:Synovial sarcoma: immunohistochemical expression of P-glycoprotein and glutathione S transferase-pi and clinical drug resistance. 911 70

Testicular anaplastic seminoma, which has a high mitotic activity, is regarded as more malignant than typical seminoma, although its prognosis is still unclear. To determine whether seminoma with relatively greater malignancy potential can be identified based on the cell proliferative activity, the mitotic rate (MR; mitotic count per high-power field), mitotic index (MI; mitotic count per 1000 cells), Ki-67 labeling index (Ki-67 LI; the percentage of positive cells) and proliferating cell nuclear antigen LI (PCNA LI; the percentage of positive cells) were histologically examined in 44 patients. The MI, Ki-67 LI and PCNA LI in patients with metastatic disease were significantly higher than those in patients without metastatic disease, and the MI in patients with fatal disease was significantly higher than those in patients cured of the disease. However, these distributions of the MI, Ki-67 LI and PCNA LI values overlapped for both pairs of groups. There were no significant differences in the MR. These results suggest that the cell proliferative activity makes a small contribution to the malignancy potential in testicular seminoma, with the activity being not necessarily indicative of metastasis and prognosis.
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PMID:Contribution of cell proliferative activity to malignancy potential in testicular seminoma. 914 22

Results of two-dimensional electrophoresis (2-DE) analyses of human breast carcinoma are described. Tumor cells were extracted and purified from breast carcinomas with different proliferative indeces and degrees of genomic stability. Cells purified from fibroadenoma tissue served as controls for benign cells. The following results were observed: (i) Analysis of samples from different areas of the same tumor showed a high degree of similarity in the pattern of polypeptide expression. Similarly, analysis of two tumors and their metastases revealed similar 2-DE profiles. (ii) In contrast, large variations were observed between different lesions with comparable histological characteristics. Larger differences in polypeptide expression were observed between potentially highly malignant carcinomas compared to comparisons of less malignant lesions. These differences were in the same order of magnitude as those observed comparing a breast carcinoma to a lung carcinoma. (iii) The levels of all cytokeratin forms resolved (CK7, CK8, CK15, and CK18) were significantly lower in carcinomas compared to fibroadenomas. (iv) The levels of high molecular weight tropomyosins (1-3) were lower in carcinomas compared to fibroadenomas. The expression of tropomyosin-1 was found to be 1.7-fold higher in primary tumors with metastatic spread to axillar lymph nodes compared to primary tumors with no evidence of metastasis (p < 0.05). (v) The expression of proliferating cell nuclear antigen (PCNA) and some members of the stress protein family (pHSP60, HSP90, and calreticulin) were higher in carcinomas. We conclude that malignant progression of breast carcinomas results in large heterogeneity in polypeptide expression between different tumors, but that some common themes such as decreased expression of cytokeratin and tropomyosin polypeptides can be discerned.
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PMID:Analysis of polypeptide expression in benign and malignant human breast lesions. 915 Sep 45

The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment of metastases.
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PMID:Immunophenotyping of human HT29 colon cancer cell primary tumours and their metastases in severe combined immunodeficient mice. 918 53

Sections from 23 primary malignant melanomas and 39 corresponding metastases were analysed for DNA content, nuclear morphometry, and proliferating cell nuclear antigen (PCNA). In 15 of 23 patients (65%) both primary and secondary tumours showed similar DNA patterns, whereas a disparity was found in the remaining eight patients (35%). The 23 primary tumours and groups of metastases (from different patients) located in skin, lymph nodes, and brain did not differ significantly in any of the variables investigated. Cox stepwise regression analysis indicated that a large variability (CV) of nuclear area in the first metastasis correlated with increased survival after recurrence (p = 0.039) as well as with survival (p = 0.031).
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PMID:Analysis of nuclear DNA and morphometry, and proliferating cell nuclear antigen in primary and metastatic malignant melanoma. 923 95

Most patients with primary melanoma are cured by local surgery, but a significant minority develop fatal metastases. The ability to identify patients with progressive disease is central to efficient management: permitting optimal deployment of adjunctive therapy and sparing the non-progressing majority the morbidity of aggressive therapy. Accurate prediction on an individual patient basis is the ideal, but the best current prognosticators permit only assignment to risk categories. Formulaic combinations of well tried correlates of outcome (gender, ulceration, depth, thickness, and mitotic rate increase accuracy of prediction, but not to personalised level. The use of large data bases against which the attributes of individual patients may be compared is useful and amalgamation of data bases will increase the availability of this approach. The development of markers of proliferation fraction (PCNA and MIB-1) and of the metastatic phenotype (PNA-receptor status) will further refine the process. Staging of disease is critical. Accuracy of staging is improved by mapping the (sentinel) lymph nodes likely to contain early tumor by lymphoscintigraphy and dye/radiomarker localisation. The application of exquisitely sensitive immunohistochemical and molecular biological techniques to biopsies from tissues likely to be the site of metastases permit assessment of clinical stage with a previously impossible degree of accuracy (ultrastaging).
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PMID:Prediction of outcome for patients with cutaneous melanoma. 926 4

Childhood kidney tumors seldom metastasize into the cranial cavity unless it is a special histological variant. We report a 4-year-old boy with multiple intracranial metastases in the left parietotemporal and right cerebellar area from primary clear cell sarcoma of the kidney without evidence of bony metastases. Metastatic tumor revealed nests of uniformly polygonal cells with clear cytoplasm demarcated by delicate fibrovascular arcades. Tumor cells were positive for vimentin and negative for cytokeratin, S-100 protein, desmin, and myoglobin. Cellular proliferation rate measured by PCNA, and Ki-67 was not significantly different between primary tumor mass and metastatic brain lesion. Expression of p53 oncoprotein was not evident in both lesions. These findings suggested that the relapse and metastasis of clear cell sarcoma of the kidney was probably due to regrowth of micro-metastases which were present at an early stage of disease.
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PMID:Intracranial metastasis from clear cell sarcoma of the kidney--a case report. 936 10

The frequency of apoptosis was determined in 102 cases of human colorectal cancer. The results were correlated with the frequency of cell proliferation and with clinicopathological characteristics such as degree of differentiation, invasiveness and metastasis. As a marker of apoptosis, intranuclear DNA strand breaks were localized with in situ nick translation (ISNT). As a marker of proliferation, proliferating cell nuclear antigen (PCNA) was localized immunohistochemically. The numbers of nuclei positive with ISNT and for PCNA per 1,000 nuclei on tissue sections were obtained. The labelling indices were compared with clinicopathological characteristics for each tumour. The ISNT labelling index of well differentiated colon carcinomas was higher than that of poorly differentiated carcinomas. Among similarly differentiated cancers, ISNT L.I. of colon carcinomas classified as Dukes A was higher than Dukes B/C, and L.I. of carcinomas which did not metastasize to lymph node or liver was higher than that of carcinomas which metastasized. The PCNA labelling index did not correlate with any of the clinicopathological characteristics or with the ISNT labelling index. The data suggest that apoptosis indices severe as a marker of tumour progression.
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PMID:Frequency of apoptosis relates inversely to invasiveness and metastatic activity in human colorectal cancer. 936 61

Telomerase has been reported to be activated in most immortal cells and human cancers. In the present study, we assessed the correlation between telomerase activity and cellular DNA ploidy level in gastric cancer. Telomerase activity was determined semiquantitatively using the telomeric repeat amplification protocol assay, a polymerase-chain-reaction-based assay, in surgical specimens of primary tumors obtained from 36 patients with gastric cancer. No correlation was observed between telomerase activity and the proliferating cell nuclear antigen labeling index. In contrast, a positive linear correlation was observed between telomerase activity and the DNA index (r = 0.59; p < 0.01). Tumor cells with aneuploid patterns showed higher telomerase activity than those with diploid patterns (27.6+/-5.8 vs. 5.8+/-1.1%; p < 0.01). Telomerase activity of tumors with liver metastases was significantly higher than activity of those without metastases (34.5+/-16.6 vs. 11.8+/-2.4; p < 0.05). There was a trend toward a lower survival rate in 9 patients with a telomerase activity of 20% or higher compared to 27 patients with telomerase activity lower than 20%. These results suggest that the telomerase activity of gastric cancer tissue may reflect the malignant potential of the tumor.
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PMID:Correlation between telomerase activity and DNA ploidy in gastric cancer. 956 59


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