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dc.contributor.advisorKurtulmuş, Yusuf-
dc.contributor.authorCan, Mesut-
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dc.description.abstractENDOMETRİAL KANSERLERDE PTEN EKSPRESYONUNUN PROGNOSTİK FAKTÖRLERLE KARŞILAŞTIRILMASI CAN M. Aydın Adnan Menderes Üniversitesi Sağlık Bilimleri Enstitüsü Tıp Fakültesi Tıbbi Biyokimya (Tıp) Programı, Yüksek Lisans Tezi, Aydın, 2019. Endometrium kanseri günümüzde kadınlarda görülen kanserler içinde dördüncü sıradadır ve Amerika’da en sık görülen kadın kanseridir. Endometriyal karsinomlar kadın genital sisteminin en sık görülen malign tümörü olup, %80-85 olguda östrojen bağımlı iken, %10-15 olguda östrojen bağımlı değildir. Endometriyal karsinomlar tip I ve tip II olmak üzere iki gruba ayrılmaktadır. Tip I endometriyal karsinomlar anovulasyon ya da östrojen replasman tedavisi öyküsüne sahip 40-60 yaşları arasındaki genç hasta grubunda görülür. Genellikle iyi diferansiye, miyometriyum invazyonu olmayan ve endometriyal hiperplazi ile ilişkili olan karsinomlardır. Tip II endometriyal karsinomlar ise hiperplazi ve östrojen fazlası ile ilişkisi olmayan saldırgan tümörlerdir. Bunlar endometriyal atrofi zemininden gelişirler. Hastalar daha çok postmenapozal dönemde olup, tip I tümörlere göre daha ileri yaştadır. Tümör supresör gen PTEN (phosphatase ve tensin homolog), endometrial kanserlerde sıklıkla mutasyona uğrayan genlerdir. PTEN, tümör supresor gendir ve mutasyon oranı %30-50’dir. PTEN, 10.kromozomun uzun kolunda (q), 23.3 pozisyonunda lokalize olup, primer hedefi PIP3 adı verilen lipid molekülü olan, bir fosfataz kodlar. PIP3, hücre büyümesi ve apoptozu regüle eden sinyal iletim yolu üzerinde çalışır. PTEN ayrıca, iki hücre iskelet proteini ile büyük homoloji gösterir. Bu da hücre adezyon ve migrasyonunda da etkili olduğuna işaret eder. PTEN’ in, tümör büyümesinde supresor, gelişim ve metastazında ise inhibitör rol oynadığı gösterilmiştir. PTEN geninde homozigot ve heterozigot delesyon olan farelerle yapılan deneyde, PTEN tümör supresor genin gelişim sırasında oldukça önemli rolü olduğu izlenmiştir. PTEN inaktivasyonunun, histomorfolojik değişikliklerin yokluğunda bile görüldüğü tanımlanmıştır. Hiperplazilerde de yaklaşık %20 oranında görülür. Bu bulgular, PTEN inaktivasyonunun, endometrioid karsinom patogenezinin erken basamaklarında etkili olduğunu düşündürmektedir. Bu çalışmada amacımız, düşük yaş aralığındaki tip 2 endometrial kanserlerde erken basamaklarda geliştiği düşünülen PTEN proteinin ekspresyonundaki değişiklikleri Real time PCR, immunohistokimyasal yöntemler ile rutin prognostik parametrelerle karşılaştırılarak, değerlendirmektir.tr_TR
dc.description.tableofcontentsKABUL VE ONAY SAYFASI i TEŞEKKÜR i İÇİNDEKİLER iii SİMGELER ve KISALTMALAR DİZİNİ v ŞEKİLLER DİZİNİ vi RESİMLER DİZİNİ vii TABLOLAR DİZİNİ viii ÖZET ix ABSTRACT xi 1. GİRİŞ 1 2. GENEL BİLGİLER 3 2.1. Uterus 3 2.1.1. Uterus embriyolojisi: 4 2.1.2. Uterus Anatomisi: 5 2.1.3. Uterus histolojisi 6 2.2. Endometrial Karsinom 9 2.2.1. Endometrial Karsinom Tip 1 9 2.2.2. Endometrial Karsinom Tip 2 10 2.3. Endometrium Kanserlerinin Derecelendirilmesi 10 2.3.1. Histolojik Derecelendirme 10 2.3.2. Nükleer Derecelendirme 11 2.3.3. FIGO Derecelendirmesi 11 2.4. Endometrial Karsinomun Moleküler ve Genetik Özellikleri 12 2.4.1 Tip 1 Endometrium Kanserlerin Moleküler ve Genetik Özellikleri 12 2.4.2. Tip 2 Endometrium Kanserlerin Moleküler ve Genetik Özellikleri 13 2.5. PTEN 14 2.6. Endometrial Karsinom ve PTEN İlişkisi 15 3.1. Materyal Toplanması ve Örneklerin Hazırlanması 16 3.2. Endometrial Karsinom’un Sınıflandırılması 17 3.3. İmmunohistokimyasal değerlendirme 17 3.4. H skorlama 18 3.5. Moleküler Analiz 18 3.5.1 RNA İzolasyonu 19 3.5.2. RNA Saflığının Belirlenmesi ve Konsantrasyon Hesaplanması 20 3.5.3. cDNA Sentezi 20 3.5.4. RT-PCR Analizi 21 3.5. İstatistiksel Analizler 22 4. BULGULAR 23 4.1. PTEN Primer Antikoru Kullanılarak İmmunohistokimyasal Yöntem ile Değerlendirme; 26 4.2. PTEN Geni Salınım Düzeylerinin RT-PCR Yöntemi ile Değerlendirilmesi 29 5. TARTIŞMA 35 6. SONUÇ ve ÖNERİLER 39 KAYNAKLAR 40 EKLER 46 ÖZGEÇMİŞ 46tr_TR
dc.publisherAydın Adnan Menderes Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbı Biyokimya Bölümütr_TR
dc.subjectEndometrium Kanser, PTEN, Real Time PCR,tr_TR
dc.titleEndometrial kanserlerde PTEN ekspresyonunun prognostik faktörlerle karşılaştırılmasıtr_TR
dc.contributor.departmentAydın Adnan Menderes Üniversitesi, Sağlık Bilimleri Enstitüsü, Tıbbı Biyokimya Bölümütr_TR
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