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  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Differential Ki67 and bcl-2 immunoexpression in solid–glandular and spindle cell components of biphasic synovial sarcoma: a double immunostaining assessment with cytokeratin and vimentin Aims: Synovial sarcoma is a malignant soft tissue of uncertain histogenesis that may show a biphasic (spindle and solid/glandular components) or a monophasic histological appearance. In previous studies, we demonstrated that the solid/glandular component possesses higher proliferation rates than the spindle cell component of biphasic synovial sarcomas and that the spindle cell component may exhibit a progressive transition from or to the solid-glandular component in biphasic synovial sarcoma. To evaluate this hypothesis further, we designed a novel approach to correlate immunoexpression of Ki67, bcl-2 and bax in the spindle cell and in the solid-glandular component of biphasic synovial sarcomas. We also performed a double-immunohistochemical assessment of the Ki67 proliferative indices and the immunoexpression of anti-apoptotic protein bcl-2 in neoplastic cells expressing either vimentin or cytokeratin. Methods and results: Immunohistochemistry for vimentin (10 cases), bcl-2 (10 cases), Ki67(10 cases), cytokeratin (10 cases), and bax (eight cases), and double-immunostaining for vimentin/Ki67 (10 cases), vimentin/bcl-2 (nine cases), cytokeratin/Ki67 (10 cases), and cytokeratin/bcl-2 (10 cases) assays were performed in 10 cases of primary biphasic synovial sarcoma. Semiquantitative assessment was adopted for each case in both components. Statistical analysis was performed using Fisher's exact test or χ2 test. On conventional immunohistochemistry, the solid/glandular component revealed more expression of Ki67, bax and cytokeratin than the spindle cell component (P=0.0004, P=0.082, and P 〈 0.0001, respectively); on the other hand, the latter showed higher expression of bcl-2 and vimentin than the former (P=0.0281 and P=0.059, respectively). Double immunohistochemistry analysis revealed higher co-expression levels of cytokeratin/Ki67 and cytokeratin/bcl-2 than the spindle cell component (P=0.015 and P 〈 0.0001, respectively); conversely, the latter presented higher co-expression of vimentin/bcl-2 than the former (P=0.0007). All cases showed no more than 10% of cells coexpressing cytokeratin/bcl-2, cytokeratin/Ki67, and no case revealed cells coexpressing vimentin/Ki67. Conclusion: Our findings indicate that in biphasic synovial sarcoma the acquisition of epithelial phenotype (solid/glandular component) is associated with a high expression of pro-apoptotic proteins and a high proliferative differentiation status, and conversely, mesenchymal phenotype (spindle cell component) is associated with a high expression of apoptosis-inhibitor bcl-2 and a low proliferative terminal-type differentiation status.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims:  The purpose of this study was to examine the occurrence of CD44 isoforms in breast carcinomas and their role in predicting clinical outcome.Methods and results:  Shock-frozen tumour tissues from 110 patients with breast carcinoma were examined by immunohistochemistry using antibodies directed against CD44s, v5, v6, v7 and v3–10. In addition, 80 of these tumours were available for quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of CD44s and CD44v6. Immunohistochemically, the positive tumours showed cytoplasmic and/or membranous staining with all antibodies. Staining results did not correlate with histological subtype, lymph node status, status of steroid receptors, tumour size or age. Neither was any correlation found for overall and disease-free survival. Quantitative real-time RT-PCR of CD44s and CD44v6, however, revealed that expression of CD44v6 mRNA was significantly associated with lower pathological grade (Pearson χ2 test P = 0.009; linear-by-linear association P = 0.003). Linear-by-linear association between CD44s mRNA expression and lower pathological grade was also seen (P = 0.02). Survival analysis with the Kaplan–Meier method demonstrated that increased CD44s mRNA expression was significantly associated with both disease-free survival and overall survival (P = 0.0185 and P = 0.0344, respectively). A similar trend for CD44v6 mRNA expression was seen in these cases, but the difference was not significant.Conclusions:  Quantitative real-time RT-PCR revealed clinical correlations of CD44s and CD44v6 mRNA expression in breast carcinomas while immunohistochemistry for the protein expression of CD44s and other CD44 variants did not. This contradictory result merits further studies concerning the clinical impact of CD44 molecules in breast carcinomas.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Expression of c-erbB-2 protein, neuron-specific enolase (NSE) and DNA ploidy was studied by immunohistochemistry and flow cytometry in formalin-fixed and paraffin-embedded specimens from 104 patients with locally advanced transitional cell carcinoma of the bladder. Positive membrane bound c-erbB-2 staining was found in 15% of the tumours, and 38% of the tumours were positive for NSE. Only one tumour stained positively for both NSE and c-erbB-2. Expression of c-erbB-2 protein and NSE was neither correlated to tumour stage nor to histopathological grade. The frequency of non-diploid tumours was 78% in 49 c-erbB-2/NSE negative tumours, 98% in 40 NSE positive tumours, and 100% in 16 c-erbB-2 positive tumours (P=0.004). Whether the c-erbB-2 expression is a useful prognostic marker in addition to other conventional parameters, remains to be shown.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: Immunohistochemistry ; nm23/NDP kinase ; Cathepsin D ; Medullary thyroid carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reduced expression of nm23/NDP kinase and increased expression of cathepsin D seem to be correlated with the high metastatic potential in a variety of malignancies. The expression of nm23/NDP kinase and that of cathepsin D have been evaluated by means of an immunohistochemical technique in paraffin-embedded tissues from 44 primary medullary carcinomas of the thyroid gland (MCT) and from the corresponding lymph node metastases in 32 of these cases. In addition, lymph node metastases from 4 cases were studied. We found that 36 of 44 (82%) primary and 26 of 36 (72%) lymph node metastatic MCT were nm23/NDP kinase positive, whereas 14 of the 44 (32%) primary and 17 of the 36 (47%) lymph node metastatic MCT were cathepsin D positive. We found no indication that the nm23/NDP kinase level has any prognostic significance in MCT. The cathepsin D level is close to being prognostically significant in this study, and we cannot exclude the possibility that it could be of prognostic value. However, it seems to be quite weak, and therefore of little use in a clinical situation.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2307
    Keywords: Key words Adenocarcinoma cell ; Mesothelial cells ; Effusions ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The detection of malignant cells in serous effusions obtained from patients diagnosed with cancer marks the presence of metastatic disease and is associated with a poor outcome. The purpose of this study was to evaluate the role of CD44s and CD44v isoforms in the distinction between mesothelial cells and malignant epithelial cells in effusions. Fifty-nine fresh pleural and peritoneal effusions were studied. These consisted of 41 specimens from patients with known gynecological neoplasms, 9 from patients diagnosed with breast adenocarcinoma, and 9 effusions from patients with various nongynecological malignancies or tumors of unknown origin. Forty-three effusions contained malignant/atypical epithelial cells, and 16 effusions were diagnosed as reactive. Three effusions contained exclusively malignant cells. Specimens were stained with anti-CD44s, v3, v5, v6, v7 and v3-10. The presence of staining in cancer cells, benign mesothelial cells and lymphocytes was evaluated. CD44s immunoreactivity was seen in 10 of 43 (23%) cases in malignant/atypical epithelial cells and in 53 of 56 (94%) cases in benign cells. In contrast, CD44v3-10 was seen in 23 of 43 (55%) cases in malignant/atypical epithelial cells and in 3 of 56 (6%) cases in benign cells. We advocate the use of CD44s and CD44v3-10 immunostaining in diagnostic evaluation of difficult serous effusions.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 436 (2000), S. 224-228 
    ISSN: 1432-2307
    Keywords: Key words Apoptosis ; bax ; bcl-2 ; Colon carcinoma ; CyclinD1 ; Immunohistochemistry ; p21 ; p53 ; pRb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Tumour growth is regulated by a balance between proliferation, growth arrest and programmed cell death (apoptosis). Until recently, the majority of the studies dealing with oncogenesis has been focused on the regulation of cell proliferation. There is now growing understanding that control of growth arrest and apoptosis play key roles in the development of human cancer and in cancer treatment. Some of the more heavily studied proteins of importance for the control of growth arrest and apoptosis are p53, p21, bcl-2 and bax. Alterations in the p53 protein may lead to malignant transformation and defect therapy response, most likely as a result of defective p53-dependent apoptosis. In addition, p21 (WAF1/CIP1) is involved in cell-cycle arrest and probably in induction of p53-dependent apoptosis. Proteins belonging to the bcl-2 family are also important for normal apoptosis. Overexpression of bcl-2 protein is thought to reduce the apoptotic capacity, while bax protein seems to be necessary for induction of apoptosis. In this study, we have immunostained tissues from 93 primary colon carcinomas and have examined the expression of p53, p21 (WAF1/CIP1), bcl-2 bax, pRb and cyclin D1 for evaluation of their roles in colon-cancer progression. A highly significant association between p53 accumulation and downregulation of p21 (WAF1/CIP1) was seen. We also found a strong association between reduced/absent p21 and the development of metastases and death due to cancer disease. Cyclin D1, bcl-2 and bax protein failed to have independent prognostic impacts. Bcl-2 and bax protein levels showed an inverse relationship. The results of the present study indicate that reduced p21 protein levels play an important role in progression of colon cancer. We concluded that evaluation of p21 expression in primary colon carcinomas at the time of surgery might be a valuable tool in defining patients with a high risk of developing metastases.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1569-8041
    Keywords: cathepsin-D ; nm23 ; ovarian cancer ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Different regulators or effectors of the metastatic cascade can be of prognostic and/or predictive significance. Cathepsin-D and nm23 operate at different levels of the metastatic process and have not yet been analyzed in combination in ovarian cancer. Patients and methods: The prevalence of cathepsin-D and nm23 expression was studied with immunohistochemistry in a cohort of 185 previously untreated cases of FIGO stage III ovarian cancer. Correlations with known prognostic factors were examined, and both uni- and multivariate survival analyses were performed. Results: Epithelial cell cathepsin-D expression was found in 58% of cases, stromal cell cathepsin-D expression in 20%, and nm23 expression in 72%. Epithelial cell cathepsin-D expression was positively correlated with better differentiation of the tumor tissue (P = 0.034). No correlation was found between epithelial and stromal cell cathepsin-D expression, but a striking degree of positive correlation was demonstrated between epithelial cell cathepsin-D and nm23 expression (P = 0.005). None of the factors studied was of any value in predicting the response to platinum and anthracyclin combination chemotherapy, as assessed by second look laparotomy. In univariate analysis age, FIGO substage, histological type, differentiation grade, ascites, residual disease and epithelial cathepsin-D were associated with corrected survival. Neither stromal cell cathepsin-D, nor nm23 expression were of prognostic significance. However, in multivariate analysis the combination of epithelial and stromal cell cathepsin-D expression (P = 0.030), residual disease (P = 0.002) and differentiation grade (P = 0.007) were the only remaining independent prognostic factors in this patient group. Conclusions: Our results support a favourable prognostic significance of cathepsin-D expression in advanced ovarian cancer, but underscore the importance of considering both epithelial and stromal cell expression. We could not confirm the prognostic significance of nm23 expression in the present cohort of advanced ovarian cancer patients.
    Type of Medium: Electronic Resource
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