Kasa invaziv mesane kanserlerinde moleküler profil ile prognoz ilişkisi
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Dosyalar
Tarih
2020
Yazarlar
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Yayıncı
Trakya Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mesane kanserleri, tanısı, tedavisi ve takibinde invaziv işlemlerin uygulandığı ve bu nedenle getirdiği mali yükün fazla olan orta sıklıkta görülen kanserlerdir. Bu tümörlerin oluşma sürecindeki moleküler mekanizmalar son yıllarda ortaya çıkarılmaktadır. Mesane kanseri patogenezinde rol oynayan genlerdeki mutasyonları ve kullanımının fayda sağlayabileceği düşünülen antikorları incelediğimiz çalışmamızda, immünohistokimyasal boyama yöntemi ile elde edilen ekspresyon durumlarının prognostik verilerle karşılaştırılması amaçlandı. Ayrıca polimeraz zincir reaksiyonu çalışması sonucu elde edilen mutasyon durumlarının hastalarda neoadjuvan tedaviye yanıt ile ilişkili olup olmadığı ve bu mutasyon durumlarının prognostik parametreler ile ilişkisinin olup olmadığı incelendi. Trakya Üniversitesi Tıp Fakültesi hastanesi patoloji laboratuvarında tanı almış ve neoadjuvan tedavi verilmiş 23 mesane kanseri olgusu çalışmaya dahil edildi. Olgulara ait klinik ve prognostik veriler onkoloji birimi aracılığıyla elde edildi. Olgulara ait Hematoksilen & Eozin kesitleri ışık mikroskobunda incelendi. Her olguya ait 1 operasyon öncesi transüretral rezeksiyon 1 tane de sistektomi materyalindeki uygun blok seçilerek Keratin 5, Keratin14, Keratin20 ve GATA3 antikorlarıyla çalışma uygulandı. Ayrıca 12 olguda Hematoksilen & Eozin kesitlerinden uygun tümör alanı seçilerek gerçek zamanlı polimeraz zincir reaksiyonu uygulandı. Preop transüretral rezeksiyon materyalinde Keratin 14 ekspresyonu olan olgularda genel sağkalım (p=0,007) ve progresyonsuz sağkalım süresinin (p=0,02) daha kısa olduğu istatistiksel yönden anlamlı olarak bulunmuştur. GATA binding protein 3 antikoru ile preop transüretral rezeksiyon materyalinde ekspresyon gösteren olgularda genel sağkalım süresi 43 ay iken, ekspresyon göstermeyen olgularda bu süre 16 ay olarak hesaplanmıştır. Bu durum istatistiksel yönden anlamlı olmasa da oldukça dikkat çekicidir. 12 olguya uygulanan ve 9 gendeki mutasyonun incelendiği moleküler çalışmalarda 3 olguda ‘tümör proteini 53’ mutasyonu ve 1 olguda ‘Fosfatidilinozitol-4,5-bisfosfat 3-kinaz katalitik subunit alfa’ mutasyonu belirlenmiştir. Moleküler çalışma sonuçları prognostik verilerle karşılaştırıldığında anlamlı sonuca ulaşılamamıştır. Sonuç olarak, Keratin 14 ve GATA3 antikorlarının beraber kullanımı preop hastalarda prognoz tahmininde rutin pratikte kullanılabileceği görülmüştür. Keratin 5 antikorunun kullanımı ile ilgili somut kanıt elde edilememiştir. Tümör proteini 53 ve Fosfatidilinozitol-4,5-bisfosfat 3-kinaz katalitik subunit alfa mutastonlarıyla ilgili daha geniş olgu sayılarını içeren moleküler incelemeye dayalı çalışmalara ihtiyaç vardır.
Bladder cancers are moderately common cancers with a high financial burden due to the invasive measures used in diagnosis, treatment and follow-up. The molecular mechanisms in development process of these tumors have recently been discovered. In our study, which examines mutations in genes playing a role in bladder cancer pathogenesis and antibodies that are considered to be helpful when used, it is aimed to compare expression situations determined using immunohistochemical staining method with prognostic data. In addition, it is examined whether the mutation situations detected using polymerase chain reaction have a relationship with the patient’s respond to neo-adjuvant therapy and prognostic parameters. Twenty three bladder cancer cases, diagnosed in Trakya University Faculty of Medicine, Laboratory of Pathology and treated with neo-adjuvant therapy, were included in the study. Clinical and prognostic data of the cases were obtained from the oncology unit. Hematoxylin & Eosin-stained tissue sections were examined using light microscopy. Two suitable blocks of each case, one pre-operational trans-urethral resection and one cystectomy material, were chosen and Keratin 5, Keratin 14, Keratin 20 and GATA binding protein 3 antibodies were applied to these sections. Also in twelve cases, suitable tumor fields chosen from Hematoxylin & Eosin-stained tissue sections were examined using real-time polymerase chain reaction. In cases showing expression of Keratin 14 in pre-operational transurethral resection material, overall survival (p=0,007) and progression-free survival (p=0,02) were found statistically significantly shorter. While overall survival period was calculated as 43 months in cases showing expression of GATA3 antibody and pre-operative transurethral resection material, it was 16 months in cases showing no expression. This situation, although not statistically significant, is quite remarkable. In the molecular studies examining mutations in nine genes in twelve cases, ‘tumor protein 53’ mutation in three cases and ‘Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha’ mutation in one case have been determined. When the results of molecular studies were compared with prognostic data, no significant results have been found. In conclusion, it is seen that the use of Keratin 14 and GATA3 antibodies together can be applied in routine practice to predict prognosis in pre-operative patients. No concrete evidence has been obtained regarding the use of Keratin 5 antibody. Further molecular studies involving higher number of cases on Tumor protein 53 and Phosphatidylinositol 4,5-bisphosphate 3kinase catalytic subunit alpha mutations are necessary.
Bladder cancers are moderately common cancers with a high financial burden due to the invasive measures used in diagnosis, treatment and follow-up. The molecular mechanisms in development process of these tumors have recently been discovered. In our study, which examines mutations in genes playing a role in bladder cancer pathogenesis and antibodies that are considered to be helpful when used, it is aimed to compare expression situations determined using immunohistochemical staining method with prognostic data. In addition, it is examined whether the mutation situations detected using polymerase chain reaction have a relationship with the patient’s respond to neo-adjuvant therapy and prognostic parameters. Twenty three bladder cancer cases, diagnosed in Trakya University Faculty of Medicine, Laboratory of Pathology and treated with neo-adjuvant therapy, were included in the study. Clinical and prognostic data of the cases were obtained from the oncology unit. Hematoxylin & Eosin-stained tissue sections were examined using light microscopy. Two suitable blocks of each case, one pre-operational trans-urethral resection and one cystectomy material, were chosen and Keratin 5, Keratin 14, Keratin 20 and GATA binding protein 3 antibodies were applied to these sections. Also in twelve cases, suitable tumor fields chosen from Hematoxylin & Eosin-stained tissue sections were examined using real-time polymerase chain reaction. In cases showing expression of Keratin 14 in pre-operational transurethral resection material, overall survival (p=0,007) and progression-free survival (p=0,02) were found statistically significantly shorter. While overall survival period was calculated as 43 months in cases showing expression of GATA3 antibody and pre-operative transurethral resection material, it was 16 months in cases showing no expression. This situation, although not statistically significant, is quite remarkable. In the molecular studies examining mutations in nine genes in twelve cases, ‘tumor protein 53’ mutation in three cases and ‘Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha’ mutation in one case have been determined. When the results of molecular studies were compared with prognostic data, no significant results have been found. In conclusion, it is seen that the use of Keratin 14 and GATA3 antibodies together can be applied in routine practice to predict prognosis in pre-operative patients. No concrete evidence has been obtained regarding the use of Keratin 5 antibody. Further molecular studies involving higher number of cases on Tumor protein 53 and Phosphatidylinositol 4,5-bisphosphate 3kinase catalytic subunit alpha mutations are necessary.
Açıklama
Anahtar Kelimeler
Mesane Kanseri, Prognoz, Neoadjuvan Tedavi, Moleküler, Keratin 14, Bladder Cancer, Prognosis, Neoadjuvant Therapy, Molecular
