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    The effect of polymorphisms in the promoter region of the MMP-1 gene on the occurrence and invasiveness of hypophyseal adenoma
    (Springer Wien, 2010) Altas, Murat; Bayrak, Omer Faruk; Ayan, Erdogan; Bolukbasi, Fatihhan; Silav, Gokalp; Coskun, Kerim Kenan; Culha, Mustafa
    The matrix metalloproteinase-1 enzyme (MMP-1, also called collagenase 1) plays a key role in turnover of collagen fibers in the intercellular matrix. Insertion of a guanine residue was found within the promoter region of the MMP-1 gene. We found that MMP-1 levels increased approximately twofold over normal when this insertion was present, enabling MMP-1 to facilitate tumor invasion and metastasis. MMP-1 is also believed to play a role in tumor development. The aim of our study is to investigate the effect of polymorphisms in the promoter region of the MMP-1 gene on the development of benign and invasive hypophyseal adenomas. Thirty patients with hypophyseal adenomas diagnosed by radiological examination underwent surgical removal, and the diagnosis was confirmed using immunohistochemical staining of the pathology specimens. We found that ten of these patients had invasive adenomas confirmed by radiological examination and immunohistochemical staining. DNA isolation was performed on all specimens, and 5-cc venous blood samples were obtained from all patients as well as 30 volunteers using the Qiagen QIAquick kit. Promoter regions of MMP-1 genes from the DNA samples were amplified using polymerase chain reaction (PCR) and primers designed for the site-directed mutation method. Following PCR, a guanine residue within the promoter region of the MMP-1 gene was identified using the restriction fragment length polymorphism method and the ALU I restriction enzyme. Three genotypes were detected in a genotyping assay: 2G/2G, 1G/2G, and 1G/1G. Of the surgically treated patients, 36.6% had the 2G/2G genotype, 46.6% had the 1G/2G genotype, and 16.6% had the 1G/1G genotype. The 2G allele frequency was found to be 83.4%. In 90% of cases of invasive adenoma, a homozygous 2G/2G genotype was detected. The risk for development of hypophyseal adenoma may be greater in patients with the 2G allele. In cases of existing hypophyseal adenoma, those with the homozygous 2G allele tend to be invasive.
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    Investigation of ACE Genome Insertion/Deletion Correlation with Immunohistochemical Profile in Pituitary Adenomas
    (Turkish Neurosurgical Soc, 2013) Altas, Murat; Bayrak, Omer Faruk; Serefhan, Alpay; Silav, Gokalp; Coskun, Kerim Kenan; Cerci, Ajlan; Isik, Nejat
    AIM: The deletion polymorphism of the angiotensin-converting enzyme (ACE) genome causes neoplastic development in several organs by increasing the angiotensin 2 (A2) formation. In this study, we aimed to identify the ACE genome insertion/deletion polymorphism in pituitary adenomas and to compare it with the control group. MATERIAL and METHODS: Patients operated for pituitary adenomas were included in the study. Genomic DNA was extracted from tumoral tissues and peripheral blood samples of the patients by using the Miller method. Primary sequence was selected via targeting the polymorphic region of intron 16 of ACE genome 17q23. DNA samples were multiplied by PCR using HACE3s and HACE3as primers. RESULTS: Twenty-one operated cases were studied. In the study group; 44% of the patients were identified as DID, 33% of them as I/D and 23% of them as I/I. In 60%, D allele was identified. According to immunohistochemical investigation, we found that 100% of the patients with Cushing adenoma were D/D alleles. CONCLUSION: Presence of high rate of ACE genome deletion in patients with pituitary adenoma and grade 3-4 patients suggest that ACE genome polymorphism can be a risk factor for the development of pituitary adenomas.
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    Microsurgical management of non-neurofibromatosis spinal schwannoma
    (Elsevier Doyma Sl, 2013) Altas, Murat; Cerci, Ajlan; Silav, Gokalp; Sari, Ramazan; Coskun, Kenan; Balak, Naci; Isik, Nejat
    Introduction: The aim of this study is to assess the clinical properties and surgical results of patients diagnosed with spinal schwannomas without neurofibromatosis (NF) properties. Patients and methods: The data obtained from 35 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. 35 patients underwent surgery for spinal schwannoma at our institution between January 1997 and 2010. The data were gathered retrospectively from medical records and included clinical presentation, tumor location and post-operative complications. All cases were surgically excised, and they were confirmed to be schwannomas by pathologists with histopathological sections in paraffin stained with hematoxylin-eosin. Result: We treated 35 (20 males and 15 females) patients with spinal schwannomas. The mean age of the patients was 47.2 (between 13 and 76) years. Of the cases, six schwannomas were located in the cervical spine, four in the thoracic spine, two in cervico-thoracic area, 10 in the thoraco-lumbar area and 13 in the lumbar spine. Two patients had malignant schwannomas that were recurrent. Of the 35 cases, the schwannomas were intradural-extramedullary in 30 cases (86%), intradural-intramedullar in 2 cases (6%), and extradural in 3 cases (9%). Conclusion: Spinal schwannomas may occur at any level of the spinal axis and are most frequently intradural-extramedullary. The most common clinical presentation is pain. Most of the spinal schwannomas in non-NF patients can be resected completely without or with minor post-operative deficits. This knowledge may help us to create a strategy for total resection of a spinal schwannomas. (C) 2011 Sociedad Espanola de Neurocirugia. Published by Elsevier Espana, S.L. All rights reserved.