ABSTRACT
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation.
Subject(s)
Aortic Aneurysm, Abdominal/metabolism , Arterial Occlusive Diseases/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinases/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Aortic Diseases/metabolism , Humans , Immunohistochemistry , Myocytes, Smooth Muscle/metabolismABSTRACT
Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.
Subject(s)
Breast Neoplasms/classification , Breast Neoplasms/diagnosis , Austria/epidemiology , Biopsy , Biopsy, Needle , Breast Neoplasms/metabolism , Female , Humans , Immunoenzyme Techniques , Middle Aged , Multicenter Studies as Topic , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Prospective Studies , Receptor, ErbB-2/metabolismABSTRACT
Recent data suggest that mast cells (MCs) and their products are involved in the pathophysiology of thrombosis. In the present study, we analyzed the number, distribution, and phenotype of prostate MCs and periprostatic MCs in patients with unilateral periprostatic vein thrombosis (PVT) by immunohistochemical analysis and electron microscopy. MCs reacted with monoclonal antibodies to tryptase, chymase, and c-kit/CD117 and stained positively for tissue-type plasminogen activator (tPA) and urokinase receptor (uPAR/CD87) but did not express detectable urokinase (uPA) or plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the mean +/- SEM number of MCs in PVT compared with control (PVT, 14.36 +/- 1.57 vs control, 5.23 +/- 0.57/mm2). The majority of MCs accumulated in the adventitia of thrombosed veins and showed a decrease in chymase expression. As MCs increase in number in PVT and express a profibrinolytic phenotype, we hypothesize that MC-derived molecules have a role in endogenous fibrinolysis.
Subject(s)
Mast Cells/pathology , Prostate/blood supply , Prostate/pathology , Venous Thrombosis/pathology , Aged , Aged, 80 and over , Austria , Cell Count , Humans , Incidence , Male , Mast Cells/physiology , Middle Aged , Phenotype , Prostate/physiopathology , Venous Thrombosis/epidemiologyABSTRACT
Downregulation of KAI1 metastasis suppressor protein is associated with dismal prognosis in a variety of cancers. Mutation of p53 was suggested to be involved in KAI1-downregulation. In cervical cancer, p53 is inactivated by human papillomavirus (HPV) oncoprotein E6 with the grade of inactivation depending on the HPV type. KAI1-expression was immunohistochemically determined in 67 specimens of cervical cancer, HPV-typing was performed using polymerase chain reaction (PCR), cloning, and sequencing. KAI1-downregulation was found in 68.1% of patients, HPV-infection in 91%. There was no association of KAI1-downregulation and infection with a particular HPV type. KAI1-downregulation in cervical cancer seems independent of HPV-E6 induced p53 inactivation.
