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Sybren L Meijer,
Jelle Wesseling,
Vincent T Smit,
Petra M Nederlof,
Gerrit K J Hooijer,
Henrique Ruijter,
Jan Willem Arends, Mike Kliffen,
Joost M van Gorp,
Lotus Sterk,
Marc J van de Vijver
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ABSTRACT: Equivocal human epidermal growth factor receptor 2 protein (HER2) (2+) immunohistochemistry (IHC) is subject to significant interobserver variation and poses a challenge in obtaining a definitive positive or negative test result. This equivocal test result group accounts for approximately 15% of all tumours, and for optimal guidance of HER2 targeted therapy, a further analysis of quantification of gene copy number and amplification status is needed for patients with early or metastatic breast cancer.
553 breast-cancer specimens with equivocal HER2 IHC(2+) test results were collected and subsequently centrally retested by chromogenic in situ hybridisation (CISH), and HER2 gene copy numbers per tumour cell nucleus were determined.
Using CISH, 77 of 553 equivocal HER2 IHC(2+) test result cases (13.9% of total) showed high levels of HER2 gene amplification (≥10.0 gene copies per nucleus), and 41 of 553 (7.4% of total) showed low-level HER2 gene amplification (6.0-9.9 gene copies per nucleus). In 73.6% of cases, no amplification of the HER2 gene was shown, and in only 4.9% of cases was an equivocal test result by CISH observed (4.0-5.9 gene copies per nucleus).
Testing by CISH of all equivocal HER2 IHC(2+) test result provides a definitive guidance in HER2 targeted therapy in 95.1% of cases. A significant proportion (21.3%) of patients with equivocal IHC(2+) test results show amplification of the HER2 gene.
Journal of clinical pathology 08/2011; 64(12):1069-72. · 2.43 Impact Factor
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ABSTRACT: Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm that most frequently affects the pleura, although it has been reported with increasing frequency in various other sites such as in the peritoneum, pericardium and in non-serosal sites such as lung parenchyma, upper respiratory tract, orbit, thyroid, parotid gland, or thymus. Liver parenchyma is rarely affected. Clinically, SFTs cause symptoms after having reached a certain size or when vital structures are involved. In recent years, SFTs are more often identified and distinguished from other tumours with a similar appearance due to the availability of characteristic immunohistochemical markers.
In this manuscript we report the case of a large tumour of the liver, which was histologically diagnosed as a SFT, and showed involvement of a single hepatic segment. Because of the patient's presentation and clinical course, it may represent a radiation-induced lesion.
When a SFT has been diagnosed, surgery is the treatment of choice. The small number of patients with a SFT of the liver and its unknown natural behaviour creates the need to a careful registration and follow-up of all identified cases.
World Journal of Surgical Oncology 02/2006; 4:81. · 1.12 Impact Factor
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ABSTRACT: Abstract
Background
Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm that most frequently affects the pleura, although it has been reported with increasing frequency in various other sites such as in the peritoneum, pericardium and in non-serosal sites such as lung parenchyma, upper respiratory tract, orbit, thyroid, parotid gland, or thymus. Liver parenchyma is rarely affected. Clinically, SFTs cause symptoms after having reached a certain size or when vital structures are involved. In recent years, SFTs are more often identified and distinguished from other tumours with a similar appearance due to the availability of characteristic immunohistochemical markers.
Case presentation
In this manuscript we report the case of a large tumour of the liver, which was histologically diagnosed as a SFT, and showed involvement of a single hepatic segment. Because of the patient's presentation and clinical course, it may represent a radiation-induced lesion.
Conclusion
When a SFT has been diagnosed, surgery is the treatment of choice. The small number of patients with a SFT of the liver and its unknown natural behaviour creates the need to a careful registration and follow-up of all identified cases
World Journal of Surgical Oncology. 01/2006;
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Archives of Ophthalmology 12/2005; 123(11):1614. · 3.71 Impact Factor
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ABSTRACT: Human testicular germ cell tumours of adolescents and adults (TGCTs), the seminomatous and non-seminomatous germ cell tumours, show morphological and biological similarities to normal embryonic development, presumably determined by their supposed cell of origin, the primordial germ cell/gonocyte. Based on this knowledge, OCT3/4, also known as POU5F1, was recently defined as a diagnostic marker for these tumour types. In the adult testis, positive immunohistochemistry for OCT3/4 is an absolute indicator for the presence of the TGCT precursor carcinoma in situ/intratubular germ cell neoplasia undifferentiated (CIS/ITGCNU), seminoma, and/or embryonal carcinoma. Several studies have confirmed this observation, using the same polyclonal antibody. The present study demonstrates the usefulness of OCT3/4 immunohistochemistry in a diagnostic setting of a consecutively collected series of more than 200 testicular tumours and over 80 testicular biopsies. Moreover, it is shown that a monoclonal antibody directed against OCT3/4 is as informative as the polyclonal antibody, both in immunohistochemistry and in western blot analysis. The antibodies are robust and applicable with different methods of pretreatment and storage of tissue. This allows routine application of this diagnostic marker.
The Journal of Pathology 07/2005; 206(2):242-9. · 6.32 Impact Factor
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ABSTRACT: The insulin-like growth factor (IGF)-I protein is a growth-promoting polypeptide that can act as an angiogenic agent in the eye. The purpose of the current study was to localize the expression of IGF-I and its receptor (IGF-IR) mRNA and IGF-IR protein in situ in the normal human eye and to examine the presence of expression in eyes with neovascular age-related macular degeneration (AMD).
Formalin-fixed, paraffin-embedded slides of 4 normal control eyes and 14 eyes with choroidal neovascularization (CNV) secondary to AMD were examined. Three eyes with proliferative diabetic retinopathy were studied as the positive control. IGF-I and IGF-IR mRNA was detected by in situ hybridization with digoxigenin-labeled RNA probes. IGF-IR protein was studied by immunohistochemistry.
In the normal retina, IGF-I and IGF-IR mRNA expression was found throughout the neuroretinal layers, in the retinal pigment epithelium (RPE), and in some choriocapillary and retinal capillary endothelial cells. In eyes with CNV we found IGF and IGF-IR mRNA in capillary endothelial cells, some transdifferentiated RPE, and fibroblast-like cells. IGF-IR protein was found in normal eyes in all neuroretinal layers, in the RPE, and in the choroidal vessels. In eyes with CNV, IGF-IR protein was present in the RPE monolayer, in transdifferentiated RPE, and in newly formed vessels.
The colocalization of protein and receptor indicates an autocrine function of IGF-I in the normal human retina. Because IGF-I participates in ocular neovascularization, synthesis of IGF-IR and IGF-I in endothelial cells, RPE cells, and fibroblast-like cells in CNV may point toward a role for this growth factor in the pathogenesis of neovascular AMD.
Investigative Ophthalmology & Visual Science 06/2003; 44(5):2192-8. · 3.60 Impact Factor
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ABSTRACT: Vascular photodynamic therapy (PDT) inhibits intimal hyperplasia (IH) induced by angioplasty in rat iliac arteries by eradicating the proliferating smooth muscle cells. This process may jeopardise the structure and strength of the arterial wall, reflected by a decreased bursting pressure.
Thirty male Wistar rats of 250-300 g were subdivided into 3 groups (n = 10). In all groups, IH was induced by balloon injury (BI). One experimental group received PDT at 50 J/cm diffuser length, the other group at 100 J/cm diffuser length. The third group served as control group and received no PDT. In half of each group the bursting pressure was analyzed after 2 hours (n = 5), in the other half after 1 year.
Two hours after the procedure the bursting pressure was 3.37 +/- 0.58 (+/-SEM) bar in the BI + PDT 50 and 3.96 +/- 0.43 bar in the BI + PDT 100 group, compared to 2.20 +/- 0.27 bar in the BI group (P < 0.05). After 1 year these values were 3.18 +/- 0.87 bar in the BI + PDT 50 (P < 0.05) and 2.02 +/- 0.31 bar in the BI + PDT 100 group, compared to 2.10 +/- 0.30 bar in the BI group (NS). In the BI + PDT 100 group, 3 out of 5 rats appeared to have aneurysmal dilatation after 1 year.
Endovascular PDT increases the arterial wall strength as measured by the bursting pressure at short-term. After 1 year, wall strength is not diminished as measured by bursting pressure, but aneurysmal dilatation nevertheless developed with 100 J/cm. dl. This may limit the use of high energy PDT.
Lasers in Surgery and Medicine 01/2003; 33(1):8-15. · 2.75 Impact Factor
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ABSTRACT: Background: Radiotherapy has recently been employed to treat patients with exudative macular degeneration in order to prevent severe visual loss. Radiotherapy affects the evolution of exudative macular degeneration directly by endothelial toxicity, leading to capillary closure, and/or indirectly through its attenuating effects on the inflammatory response, mediated by macrophages and other inflammatory cells. Methods: In this study we describe the histopathologic findings in a patient with exudative age-related macular degeneration (AMD) in both eyes whose right eye was treated with radiotherapy (5 times 2 Gy) 3 years before he died. The eyes were enucleated post mortem and investigated by light microscopy. Additionally, immunohistochemical investigation with antibodies against CD34 and CD68 was performed to identify patent endothelial cells and macrophages. Results: Both eyes showed neovascular AMD consisting of mixed fibrocellular and fibrovascular membranes. Capillaries in both the choriocapillaris and the neovascular membrane were patent in both eyes. Macrophages were present in the choroidal neovascularization of both eyes. Neither preexistent choroidal, intraretinal, nor neovascular vessels showed increased wall thickness as sign of radiation damage. Conclusion: No radiation-related histopathologic effect could be demonstrated 3 years after radiation therapy in this patient with AMD.
Albrecht von Graæes Archiv für Ophthalmologie 06/2001; 239(7):539-543. · 2.17 Impact Factor
