Normal prostat, yüksek dereceli prostatik intraepitelyal neoplazi ve prostat adenokarsinomlarında BRCA1, BRCA2 ve rad51 gen mutasyonlarının ummunohistokimyasal değerlendirmesi
Yükleniyor...
Dosyalar
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Prostat kanseri erkeklerde en sık görülen kanser olup kansere bağlı ölümlerde ikinci sıradadır. En sık izlenen tipi asiner adenokarsinomlardır. “Breast Cancer Suscebtibility” genlerinde oluşan germline ve somatik mutasyonların gerek ailesel meme ve prostat kanseri gelişimiyle gerekse sporadik birçok tümörün oluşumunda rol aldığı çok sayıda çalışmayla gösterilmiştir. Bu genlerin ve Deoksiribonükleik asit tamir mekanizmalarında bu genlerle birlikte rol aldığı bilinen RAD51’in bir arada değerlendirildiği ve ilişkilerinin incelendiği çalışma sayısı az olup, bunların büyük bir kısmı genetik temelli çalışmalardır. Bu çalışmada normal prostat dokusunda, yüksek dereceli prostatik intraepitelyal neoplazi içeren dokuda ve malign dokuda BRCA1, BRCA2 ve RAD51 proteinlerinin, karsinogenez sırasında Deoksiribonükleik asit tamir mekanizmalarında meydana gelen bozukluklar sonucunda değişen ekspresyonlarının incelenmesi ve birbirleriyle ilişkilerinin ortaya konması amaçlandı. Bu doğrultuda çalışmaya Trakya Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı arşivinden 74 malign, 44 yüksek dereceli prostatik intraepitelyal neoplazi ve 112 benign prostat dokusu içeren toplam 230 materyal dahil edildi. Malign olgular kendi aralarında Gleason skorlarına göre üç gruba ayrıldı. Ayrıca malign olgularda bilateral tutulum, ekstraprostatik yayılım, perinöral invazyon, veziküla seminalis invazyonu ve lenfovasküler invazyon varlığı değerlendirildi. Olgulara yapılan yeni kesitlere immünohistokimyasal olarak BRCA1, BRCA2 ve RAD51 antikorları uygulandı ve iki gözlemci tarafından ışık mikroskobu altında değerlendirildi. Elde edilen verilere göre malign olgularda her üç antikorun nükleer pozitifliği yüksek dereceli prostatik intraepitelyal neoplazi ve benign gruba göre artmış olarak tespit edilmiştir. BRCA1 ve RAD51 ile bu ilişki istatistiksel olarak anlamlı izlenmiştir. Ayrıca her üç antikordaki sitoplazmik boyanma yoğunlukları, malign ve yüksek dereceli prostatik intraepitelyal neoplazi gruplarında, benign gruba göre artmış olarak izlenmiş ve istatistiksel olarak anlamlı bulunmuştur. Her üç antikorun olgu gruplarında birbirleriyle olan ilişkileri istatistiksel olarak anlamlı bulunmuştur. Malign olgu grubunda her üç antikorda izlenen nükleer pozitiflik oranının Gleason skor artışı ile paralellik gösterdiği saptanmış, istatistiksel olarak BRCA1 ve BRCA2 için bu ilişki anlamlı bulunmuştur. Malign olgular ele alındığında Gleason skoru 7 ve üzerinde olan olgularda prognostik parametrelerden olan bilateral tutulum, ekstraprostatik yayılım, perinöral invazyon, veziküla seminalis invazyonu ve lenfovasküler invazyon varlığı artmış olarak izlenmiştir. RAD51 antikorunun nükleer ve sitoplazmik boyanma değerlerindeki artışın, malign olgularda prognostik parametrelerin varlığındaki artışla ilişkili olduğu gözlenmiş, ancak lenfovasküler invazyon dışında istatistiksel olarak anlamlı ilişki tespit edilememiştir.
Abstract
Prostate cancer is the most common cancer in men and the second most common cause of death depending on cancer. Acinar adenocarcinoma is the most common type. There are number of studies about role of germline and somatic mutations in BRCA genes, either in familial and sporadic cancers. Whereas there are few studies, that evaluate of each BRCA1, BRCA2 and RAD51, which is interact with BRCA genes in DNA repair pathways. Most of these studies based on genetic assesment . The aim of current study is to research alterations in expressions of BRCA1, BRCA2 and RAD51 preoteins in malignant prostate tissues, in normal prostate tissues and in prostate tissues with high grade prostatic intraepithelial neoplasia, depending on disorders in DNA repair mechanism during carcinogenesis. Research is performed on a total number of 230 cases, which consists 74 malignant prostate tissues, 112 benign prostate tissues and 44 prostate tissues with high grade prostatic intraepithelial neoplasia. Cases are selected from the archive of Trakya University Medical Faculty Pathology Department. Malignant cases are graded and grouped into three groups with regard to Gleason scoring system. In addition malignant cases are evaluated for the presence of prognostic factors such as bilateral lobe invasion, extraprostatic extention, perineural invasion, vesicula seminalis invasion and lymphovaskular invasion. Immunohistochemical studies performed on the sections of cases and light microscopy was performed by two observers. Nuclear positivity of BRCA1, BRCA2 and RAD51 antibodies were almost similar in high grade prostatic intraepithelial neoplasia cases and benign cases, but there was significant increase in malignant cases. This relation observed statistically significant for BRCA1 and RAD51 antibodies. Also there were statistically significant increase in cytoplasmicexpressions of BRCA1, BRCA2 and RAD51 antibodies in malignant and high grade prostatic intraepithelial neoplasia cases compared with benign cases. Icreases in nuclear expression rates of three antibodies were parallel with increases in Gleason scores of tumours. This relation was proved statistically for BRCA1 and BRCA2 antibodies. Cases in malignant group, which has Gleason score 7 or higher, had statistically significant relation with the presence of prognostic factors, than cases which has Gleason score lower than 7. In addition it was observed that, nuclear and cytoplasmic expression rates of RAD51 increas with presence of prognostic factors in malignant cases. But they couldn’t be demonstrated statistically, except the relation with lymphovasculary invasion.
Abstract
Prostate cancer is the most common cancer in men and the second most common cause of death depending on cancer. Acinar adenocarcinoma is the most common type. There are number of studies about role of germline and somatic mutations in BRCA genes, either in familial and sporadic cancers. Whereas there are few studies, that evaluate of each BRCA1, BRCA2 and RAD51, which is interact with BRCA genes in DNA repair pathways. Most of these studies based on genetic assesment . The aim of current study is to research alterations in expressions of BRCA1, BRCA2 and RAD51 preoteins in malignant prostate tissues, in normal prostate tissues and in prostate tissues with high grade prostatic intraepithelial neoplasia, depending on disorders in DNA repair mechanism during carcinogenesis. Research is performed on a total number of 230 cases, which consists 74 malignant prostate tissues, 112 benign prostate tissues and 44 prostate tissues with high grade prostatic intraepithelial neoplasia. Cases are selected from the archive of Trakya University Medical Faculty Pathology Department. Malignant cases are graded and grouped into three groups with regard to Gleason scoring system. In addition malignant cases are evaluated for the presence of prognostic factors such as bilateral lobe invasion, extraprostatic extention, perineural invasion, vesicula seminalis invasion and lymphovaskular invasion. Immunohistochemical studies performed on the sections of cases and light microscopy was performed by two observers. Nuclear positivity of BRCA1, BRCA2 and RAD51 antibodies were almost similar in high grade prostatic intraepithelial neoplasia cases and benign cases, but there was significant increase in malignant cases. This relation observed statistically significant for BRCA1 and RAD51 antibodies. Also there were statistically significant increase in cytoplasmicexpressions of BRCA1, BRCA2 and RAD51 antibodies in malignant and high grade prostatic intraepithelial neoplasia cases compared with benign cases. Icreases in nuclear expression rates of three antibodies were parallel with increases in Gleason scores of tumours. This relation was proved statistically for BRCA1 and BRCA2 antibodies. Cases in malignant group, which has Gleason score 7 or higher, had statistically significant relation with the presence of prognostic factors, than cases which has Gleason score lower than 7. In addition it was observed that, nuclear and cytoplasmic expression rates of RAD51 increas with presence of prognostic factors in malignant cases. But they couldn’t be demonstrated statistically, except the relation with lymphovasculary invasion.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
RAD51, Adenokarsinom, Prostat, BRCA2, BRCA1, Prostate, Adenocarcinoma
