Diffüz büyük B hücreli lenfoma vakalarında immunhistokimyasal biomarkerların prognostik önemi
Küçük Resim Yok
Tarih
2013
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Cumhuriyet Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Diffüz büyük B hücreli lenfoma, non-Hodgkin lenfomalar içerisinde en sık görülen tiptir ve yeni tanı vakaların yaklaşık olarak %30-40?ını oluşturur. Diffüz büyük B hücreli lenfoma hem klinik hem de morfolojik olarak heterojen bir hastalıktır. İlk gen ifade profili çalışmaları, kemoterapi yanıtları ve total yaşam süreleri farklı iki alt grubun varlığını göstermiştir. Bunlardan birincisi; germinal merkez B hücre benzeri gen profili taşıyan grup, diğeri ise aktive B hücre benzeri gen profili taşıyan gruptur. Daha sonra cDNA mikro dizi analizi kullanılarak germinal merkez B hücre benzeri, aktive B hücre benzeri ve tip 3 gen ifade profili olan diffüz büyük B hücreli lenfoma varlığı ortaya konmuştur. Germinal merkez B hücre benzeri grubun aktive B hücre benzeri grubuna göre daha iyi yaşam süresine sahip olduğu gösterilmiştir. Tip 3 gen profili de heterojen bir grup olup aktive B hücre benzeri grubu gibi kötü prognoza sahiptir. Rutin klinik pratikte moleküler yöntemlerin uygulama güçlüğü nedeniyle immunhistokimyasal yöntemler ile bu genetik profile uygun grupların oluşturulması planlanmıştır. Bizim amacımız da kliniğimize başvurup diffüz büyük B hücreli lenfoma tanısı almış hastaların moleküler alt tiplerini belirlemek ve prognoz üzerindeki etkisini retrospektif olarak değerlendirmektir. Bu amaçla 40 hastanın biyopsi örnekleri CD10, Bcl-6 ve MUM-1 monoklonal antikor immun boyaları ile boyandı. 6 (%15) hastanın germinal merkez B hücre benzeri, 34 (%85) hastanın da germinal merkez B hücre dışı fenotipe sahip olduğu saptandı. Hastaların verileri retrospektif olarak değerlendirilerek tüm sağkalım 24.87 ay (min: 1 ay; max: 76 ay) ve olaysız sağkalım 21.97 ay (min: 0 ay; max: 68 ay) olarak hesaplandı. Germinal merkez B hücre benzeri fenotipte tüm sağkalım 31.00±15.49 ay ve olaysız sağkalım 27.66±17.95 ay iken, germinal merkez B hücre dışı fenotipte tüm sağkalım 23.79±17.82 ay ve olaysız sağkalım 20.97±17.12 ay olarak bulunmuştur. Her ne kadar bu iki fenotip ile tüm sağkalım ve olaysız sağkalım arasındaki ilişki istatistiksel olarak anlamlı bulunmasa da germinal merkez B hücre fenotipinde yaşam sürelerinin daha uzun olduğu net olarak görülmektedir. Bu alt grupların hem klinik seyri hem de kemoterapi sonrası survey oranları çok farklıdır. Eğer bu immunhistokimyasal markerlar ileride standardize edilebilirse hastaların risk profili daha net ayırt edilebilecektir. Böylelikle tanı anında agresif tedaviye veya deneysel tedaviye uygun hastalar ayırt edilerek daha doğru tedavi şemaları oluşturulabilecektir. Ayrıca, şunu da söylemeliyiz ki, Türkiye?de bu tarz epidemiyolojik çalışmaların sayısı oldukça sınırlı olduğundan, çalışmamız bu alanda ilkler arasında yer almakta ve bu nedenle de ikincil bir önem kazanmaktadır.
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma and accounts for 30% to 40% of new diagnoses. Diffuse large B-cell lymphoma is heterogeneous both clinically and morphologically. The first gene expression studies have identified two different subgroups with chemotherapy responses and total life span. The first group is of which carries germinal center B-cell-like profile, and the other one is activated B-cell-like profile. Later, it has been demonstrated by using cDNA micro array analysis that diffuse large B-cell lymphoma have germinal center B-cell-like, activated B-cell-like and type 3 gene expression profiles. It has been shown that the germinal center B-cell-like group has a significantly better survival than the activated B-cell-like group. The type 3 gen profile is a heterogeneous group and has a poor outcome similar to the activated B-cell-like group. Because of these molecular methods has practical difficulties in routine clinical practice, it has been planned to form groups appropriate to this genetic profile by immunohistochemical methods. Our aim is to determine the molecular subgroups of patients whom referred to our clinic and diagnosed with diffuse large B-cell lymphoma and to evaluate the effect of these subgroups on prognosis retrospectively. For this purpose, the biopsy specimens of 40 patients have stained with monoclonal antibody immunstains of CD10, Bcl-6 ve MUM-1. It has been established that 6 (15%) patients have germinal center B-cell-like and 34 (85%) patients have non-germinal center B-cell-like phenotypes. By evaluating the patients data retrospectively, was calculated overall survival as 24.87 months (min: 1 month; max: 76 months) and event-free survival as 21.97 months (min: 0 month; max: 68 months). While overall survival was 31.00±15.49 months and event-free survival was 27.66±17.95 months in germinal center B-cell-like phenotype, was overall survival and event-free survival as 23.79±17.82 months and 20.97±17.12 months in non-germinal center B-cell-like phenotype, respectively. Although the association between these two phenotypes and overall survival and event-free survival have not been found significant by statistically, the life span is so long in germinal center B-cell-like phenotype can be visualized clearly. Both clinical progress and survey rates after chemotherapy of these subgroups are so different. If these immunohistochemical markers can be standardized in the future, the risk profiles of the patients will be differentiated clearly. In this way, by discriminating the patients whom appropriate to aggressive or experimental therapy at diagnose, more accurate treatment schedules will have been established. Moreover, we have to say that similarly epidemiologic studies are rather limited in number in Turkey, our study has a front place in this field and so it has an increase in importance secondary.
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma and accounts for 30% to 40% of new diagnoses. Diffuse large B-cell lymphoma is heterogeneous both clinically and morphologically. The first gene expression studies have identified two different subgroups with chemotherapy responses and total life span. The first group is of which carries germinal center B-cell-like profile, and the other one is activated B-cell-like profile. Later, it has been demonstrated by using cDNA micro array analysis that diffuse large B-cell lymphoma have germinal center B-cell-like, activated B-cell-like and type 3 gene expression profiles. It has been shown that the germinal center B-cell-like group has a significantly better survival than the activated B-cell-like group. The type 3 gen profile is a heterogeneous group and has a poor outcome similar to the activated B-cell-like group. Because of these molecular methods has practical difficulties in routine clinical practice, it has been planned to form groups appropriate to this genetic profile by immunohistochemical methods. Our aim is to determine the molecular subgroups of patients whom referred to our clinic and diagnosed with diffuse large B-cell lymphoma and to evaluate the effect of these subgroups on prognosis retrospectively. For this purpose, the biopsy specimens of 40 patients have stained with monoclonal antibody immunstains of CD10, Bcl-6 ve MUM-1. It has been established that 6 (15%) patients have germinal center B-cell-like and 34 (85%) patients have non-germinal center B-cell-like phenotypes. By evaluating the patients data retrospectively, was calculated overall survival as 24.87 months (min: 1 month; max: 76 months) and event-free survival as 21.97 months (min: 0 month; max: 68 months). While overall survival was 31.00±15.49 months and event-free survival was 27.66±17.95 months in germinal center B-cell-like phenotype, was overall survival and event-free survival as 23.79±17.82 months and 20.97±17.12 months in non-germinal center B-cell-like phenotype, respectively. Although the association between these two phenotypes and overall survival and event-free survival have not been found significant by statistically, the life span is so long in germinal center B-cell-like phenotype can be visualized clearly. Both clinical progress and survey rates after chemotherapy of these subgroups are so different. If these immunohistochemical markers can be standardized in the future, the risk profiles of the patients will be differentiated clearly. In this way, by discriminating the patients whom appropriate to aggressive or experimental therapy at diagnose, more accurate treatment schedules will have been established. Moreover, we have to say that similarly epidemiologic studies are rather limited in number in Turkey, our study has a front place in this field and so it has an increase in importance secondary.
Açıklama
Enstitüler, Sağlık Bilimleri Enstitüsü, İç Hastalıkları Ana Bilim Dalı
Anahtar Kelimeler
Hematoloji, Hematology
