ABSTRACT
Epigenetic alterations have been implicated in cancer development. DNA methylation modulates gene expression, which is catalyzed by DNA methyltransferases (DNMTs). The objective of our study was to evaluate expression of DNMTs in medulloblastoma and analyze its correlation with clinical features. Nuclear expression of DNMT1, DNMT3A and DNMT3B was analyzed in human primary medulloblastoma of 44 patients using immunohistochemistry. Correlation of expression of DNMT levels with classical histological subtypes, novel molecular subgroups and survival of patients was analyzed. Elevated expression of DNMT1, DNMT3A and DNMT3B was observed in 63.64%, 68.18% and 72.73% of all cases, respectively. None of them showed a correlation with classical histology or survival. Concerning molecular subtypes, significantly higher expression of DNMT1 was observed in the SHH group compared to non-SHH samples (p = 0.02), but without significant difference in DNMT3A or DNMT3B levels between any subtypes. In conclusion, DNMT1, DNMT3A and DNMT3B are highly expressed in human medulloblastoma samples, suggesting that promoter hypermethylation may play a role in medulloblastoma development. Demethylation of tumor suppressor gene promoters may be considered as a possible future target in therapy of medulloblastoma.
Subject(s)
Cerebellar Neoplasms/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic/genetics , Medulloblastoma/genetics , Adolescent , Adult , Cerebellar Neoplasms/enzymology , Cerebellar Neoplasms/pathology , Child , Child, Preschool , DNA/genetics , DNA (Cytosine-5-)-Methyltransferase 1 , DNA Methylation/physiology , DNA Methyltransferase 3A , Female , Humans , Immunohistochemistry/methods , Infant , Male , Medulloblastoma/diagnosis , Medulloblastoma/enzymology , Medulloblastoma/pathology , Young Adult , DNA Methyltransferase 3BABSTRACT
BACKGROUND AND PURPOSE: Treatment of giant fusiform aneurysms with flow diverters has been associated with a relatively high rate of complications. Our goal was to study the evolution of flow-diverter endothelialization and thrombus organization at different time points after flow-diverter treatment in giant fusiform aneurysms to better understand reasons for flow-diverter thrombosis and delayed aneurysm ruptures. MATERIALS AND METHODS: Two giant anterior and 2 posterior circulation aneurysms, all of which had partially thrombosed before treatment, were studied. An unruptured, untreated posterior circulation aneurysm was used as a control. Each specimen was removed at 7 days or at 6, 9, or 13 months after flow-diverter treatment. The 3 patients who survived longer than 7 days were followed up by angiography and MR imaging. Formaldehyde-fixed paraffin-embedded sections were stained by using H&E, Van Gieson elastic, CD34, h-Caldesmon, and Picrosirius stains and studied by light microscopy. RESULTS: According to angiography, aneurysms were found to be obliterated partially at 6 and 9 months and completely at 13 months. MR imaging revealed that mass effect remained unchanged in each case. Sections of the flow diverter within the normal parent artery were covered by an endothelialized fibrous layer as early as 6 months, but there was no tissue coverage or endothelialization seen even at 13 months inside the aneurysm itself. Each treated aneurysm had a thin wall with complete lack of smooth muscle cells. No signs of thrombus organization were found at any of the time points studied. CONCLUSIONS: Endothelialization of the flow diverter in giant fusiform aneurysms may not occur and thrombus organization may not be initiated inside these aneurysms for as long as 1 year, which explains delayed flow-diverter thrombosis and the possibility of delayed ruptures.
Subject(s)
Endovascular Procedures/instrumentation , Intracranial Aneurysm/surgery , Stents/adverse effects , Thrombosis/epidemiology , Adult , Aged , Aneurysm, Ruptured/diagnostic imaging , Aneurysm, Ruptured/surgery , Angiography , Female , Humans , Intracranial Aneurysm/diagnostic imaging , Male , Middle Aged , Thrombosis/diagnostic imagingABSTRACT
The ultrasound guided percutaneous fine needle biopsy (US-FNAB) of focal lesions in the liver is indispensable in many clinical situations. During the last 12 years, 657 US-FNAB were performed on patients with suspected neoplastic involvement of the liver with 22-gauge Chiba needles at our department. US-FNAB was performed mostly with the "free hand" technique. Sufficient material for cytologic analysis was obtained in 84% of the cases. The biopsies confirmed malignancy in 39.3%, including 9% primary hepatocellular carcinoma, 8% of the cases were suspect for malignancy, and in 36.7% were diagnosed benign lesion. 233 cases were confirmed histologically and with other follow up methods. The sensitivity rate was 91%, and specificity was 100%. There was no false positive diagnosis and no noteworthy complications were observed. US-FNAB is a highly reliable, safe, inexpensive and easy diagnostic procedure. On the basis of our experience, we recommend US-FNAB as a routine, first level procedure for the diagnosis of focal liver diseases.
