| 11. |
- Kärjä, Vesa, et al.
(författare)
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Does protein expression predict recurrence of benign World Health Organization grade I meningioma?
- 2010
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 41:2, s. 199-207
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the predictive value of recurrence of protein expression in surgical samples of meningiomas. Thus, the expression of proteins that have been reported to be associated with prognosis of meningiomas was assessed in a sample of 59 World Health Organization grade I tumors obtained after Simpson grade I to III surgical resection (complete excision) and that were followed for 6 to 16 years. The expression was investigated applying immunohistochemical and tissue microarray techniques. One protein, the hepatocytic growth factor receptor, of 22 investigated proteins, showed significantly differing expression when comparing the 38 nonrecurrent with the 21 recurrent World Health Organization grade I meningiomas. It is noteworthy however that by means of logistic regression analyses, the independent predictive value of this protein expression was not significantly associated with the recurrence. Furthermore, it is noteworthy that the proliferation rate estimated by means of Ki67 expression did not show a significant difference, being 3.3 +/- 0.4 for the nonrecurrent meningioma and 3.9 +/- 0.5 for the recurrent and ranging from 0% to 10%. A significant and differing Spearman rank order of correlation was noted between 19 pairs of the investigated proteins when comparing nonrecurrent with recurrent World Health Organization grade I meningiomas. None of these correlations, however, showed a significant association by means of logistic regression analyses. Our results indicate that the Simpson grade significantly alters the outcome of a World Health Organization I grade meningioma and a longer follow-up period significantly increases the risk of recurrence. The expression of none of the proteins or correlation between protein expressions previously reported to be of significance regarding recurrence can be recommended as a diagnostic tool while assessing the risk of recurrence of World Health Organization grade I meningiomas.
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| 12. |
- Lucas, S D, et al.
(författare)
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Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma.
- 1996
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Ingår i: Human Pathology. - 0046-8177 .- 1532-8392. ; 27:12, s. 1329-1335
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Tidskriftsartikel (refereegranskat)abstract
- Despite its predilection for multifocal growth and regional metastasis, papillary thyroid carcinoma (PTC) is a clinically indolent malignancy with an exceptionally favorable long-term prognosis. Together with the often striking inflammatory reaction present in PTC, its quiescent behavior has been suggested to reflect the activation of a tumor-induced immune response. To examine this possibility, we have studied the deposition of immunoglobulins and complement in PTC tissue. Samples from 70 cases of neoplastic and autoimmune thyroid diseases, including PTC (n = 41), follicular, anaplastic, and medullary carcinomas (n = 12), follicular adenoma (n = 6), Graves' disease (n = 8), and Hashimoto's thyroiditis (n = 3) were analyzed immunohistochemically. Cellular deposits of immunoglobulin G (IgG), particularly subclasses IgG1 and IgG4, and complement factors C3d, C4d, and C5 were shown in up to 80% of the PTC cases, whereas the other thyroid diseases studied showed little or no cellular deposition. Nonneoplastic tissue of PTC-containing thyroid glands (n = 22) lacked staining for IgG in 50% of the cases, and 82% were devoid of complement. The results suggest a tumor-specific immune response in PTC with activation of the classical complement cascade.
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| 13. |
- Mirastschijski, Ursula, et al.
(författare)
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Ectopic localization of matrix metalloproteinase-9 in chronic cutaneous wounds.
- 2002
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 33:3, s. 355-364
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that excessive activity of matrix metalloproteinases (MMPs), in particular the gelatinases MMP-9 and MMP-2, contributes to poor healing of chronic skin ulcers. We compared MMP-9 and MMP-2 in wound margin biopsies of standardized acute partial-thickness wounds in healthy volunteers (n = 6) and in venous leg ulcer patients (n = 12) with those of chronic wounds of different etiologies (n = 34) by a combination of specific analyses of activity and protein localization. We also studied MMP-14 by immunohistochemistry and in situ hybridization in parallel. Neither MMP-9 (P =.814) nor MMP-2 (P =.742) endogenous activities differed significantly between acute and chronic wound tissues. Acute wound healing was characterized by induction of MMP-9 in the advancing epithelium. In chronic wounds, prominent MMP-9 immunostaining was seen in neutrophils and macrophages in the ulcer bed, but virtually no MMP-9 was detected in wound edge keratinocytes. MMP-2 was increased and activated with acute wound age. MMP-2 was found abundantly in dermal fibroblasts and endothelial cells beneath, but not in new epithelium of acute and chronic wounds. MMP-14 mRNA or protein was detected solely in the stroma of both acute and chronic wounds. In conclusion, the overall activity of gelatinases MMP-9 and MMP-2 was not increased in chronic wounds compared to normally healing wound tissues. Chronic nonhealing wounds may not be caused by excessive gelatinase activity, but are distinguished from healing wounds by an unfavorable distribution and persistance of MMP-9.
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| 14. |
- Mirtti, Tuomas, et al.
(författare)
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Nuclear Stat5a/b predicts early recurrence and prostate cancer-specific death in patients treated by radical prostatectomy
- 2013
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 44:3, s. 310-319
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for reliable markers to identify patients whose prostate cancer (PCa) will recur after initial therapy and progress to lethal disease. Gleason score (GS) is considered the most accurate predictive marker for disease-specific mortality after primary treatment of localized PCa. Most PCas cluster into groups of GS 6 and 7 with considerable variation in the disease recurrence and disease-specific death. In preclinical PCa models, Stat5a/b promotes PCa growth and progression. Stat5a/b is critical for PCa cell viability in vitro and for tumor growth in vivo and promotes metastatic dissemination of cancer in nude mice. Here, we analyzed the predictive value of high nuclear Stat5a/b protein levels in 2 cohorts of PCas: Material I (n = 562) PCas treated by radical prostatectomy (RP), and Material II (n = 106) PCas treated by deferred palliative therapy. In intermediate GS PCas treated by radical prostatectomy, high levels of nuclear Stat5a/b predicted both early recurrence (univariable analysis; P < .0001, multivariable analysis; HR = 1.82, P = .017) and early PCa-specific death (univariable analysis; P = .028). In addition, high nuclear Stat5a/b predicted early disease recurrence in both univariable (P < .0001) and multivariable (HR = 1.61; P = .012) analysis in the entire cohort of patients treated by RP regardless of the GS. Patients treated by deferred palliative therapy, elevated nuclear Stat5a/b expression was associated with early PCa-specific death by univariable Cox regression analysis (HR. = 1.59; 95% CI = [1.04, 2.44]; P = .034). If confirmed in future prospective studies, nuclear Stat5a/b may become a useful independent predictive marker of recurrence of lethal PCa after RP for intermediate GS PCas. (c) 2013 Elsevier Inc. All rights reserved.
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| 15. |
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| 16. |
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| 17. |
- Pierceall, William E, et al.
(författare)
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Utilization of fluorescence in situ hybridization with cytokeratin discriminators in TOP2A assessment of chemotherapy-treated patients with breast cancer
- 2012
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Ingår i: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 43:9, s. 1363-1375
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Tidskriftsartikel (refereegranskat)abstract
- Tumor biomarkers increasingly provide information for predicting outcomes with chemotherapeutic regimens (personalized medicine). Topo2A is a DNA helicase targeted by anthracyclines, cytotoxic therapeutics used in both adjuvant and palliative treatments of breast cancer. TOP2A gene amplification/deletion is implicated in response to anthracycline-based chemotherapy. We describe an approach for analyzing formalin-fixed, paraffin-embedded breast tumors on tissue microarrays with TOP2A fluorescence in situ hybridization coupled with cytokeratin immunofluorescence to target tumor cells. Stained tissue from patient specimens was imaged and analyzed using Metafer/Metacyte (Metasystems, Waltham, MA, USA), including customized image classifiers. TOP2A/CEN17 ratios of 2.0 or greater (amplified) and 0.8 or less (deleted) were observed for 10.0% and 6.1% of the patients, respectively. Patient outcomes for adjuvant chemotherapy (cyclophosphamide-epirubicin-fluorouracil, cyclophosphamide-methotrexate-fluorouracil, no chemotherapy) were evaluated. No statistical significance was achieved for clinical end points regarding TOP2A status in anthracycline-treated patients. However, patients with TOP2A aberrations receiving methotrexate-based therapy exhibited a significant decrease in 5-year distant disease-free survival and breast cancer-specific overall survival, especially for patients with TOP2A deletions (disease-free survival: hazard ratio, 5.31 [P = .001], and breast cancer-specific overall survival: hazard ratio, 6.45 [P ≤ .001]). No significant differences were seen in patients included in the no-chemotherapy group. Topo2A protein levels were assessed by immunohistochemistry with no correlative statistical relevance to immunofluorescence/fluorescence in situ hybridization-based prognosis for cyclophosphamide-epirubicin-fluorouracil or cyclophosphamide-methotrexate-fluorouracil groups. Interestingly, aberrant (under)expressing patients in the no-chemotherapy group exhibited better 5-year distant disease-free survival (hazard ratio, 0.39; P = .004), trending toward more favorable breast cancer-specific overall survival (hazard ratio, 0.61; P = .11). Our results indicate a strategy by which fluorescence in situ hybridization scoring targeted to cytokeratin-positive tumor cells may provide a tool for added precision and efficiency in TOP2A evaluation from tumor tissue.
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| 18. |
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| 19. |
- Rudolph, Pierre, et al.
(författare)
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Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer
- 2001
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 32:3, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Simultaneous overexpression of c-erbB-2 and p53 has been reported to be prognostically unfavorable in breast cancer. Herein, we show that concurrent overexpression of these 2 proteins is associated with a marked reduction in the relative fraction of cells in G(1) phase of the cell cycle, indicating an accelerated cell cycle progression. Using an immunohistochemical approach, we examined 261 cases of node-negative infiltrating ductal carcinomas of the breast with respect to c-erbB-2 and p53 expression and to the proliferative activity measured by the Ki-67 index. By means of a novel monoclonal antibody, Ki-S2, which exclusively recognizes proliferating cells in the S, G(2), and M phases of the reproductive cycle, we were further able to calculate the relative fraction of the cells having passed the restriction point at the G(1)/S boundary, thus defining a cycling ratio (CR). The results were correlated with clinical outcome; median follow-up time was 96 months. Tumors that simultaneously overexpressed c-erbB-2 and p53 had a high median CR and followed an unfavorable course. However, increased CRs were also observed independently of c-erbB-2 and p53 overexpression, suggesting that other molecular mechanisms may contribute to acceleration of cell cycle progression. In a multivariate analysis that included patient age, tumor size, hormone receptor status, c-erbB-2 and p53 expression, and the Ki-67 index, CR emerged as the most significant independent predictor of overall and disease-free survival (P <.0001). It is concluded that the CR is a gauge of cell cycle deregulation and therefore may be a powerful indicator of the biologic behavior of cancers.
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| 20. |
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