Aydın İŞİSAĞ, Nalan NEŞE, Ülkü ERGENE, Demet KOCATEPE ÇAVDAR

KRONİK LENFOSİTİK LÖSEMİ / KÜÇÜK LENFOSİTİK LENFOMADA ZAP-70, CD38 VE FAS/FAS LİGAND EKSPRESYONUNUN KEMİK İLİĞİ TUTULUM PATERNLERİYLE İLİŞKİSİ VE PROGNOSTİK DEĞERİ

Amaç: Bu çalışma, kronik lenfositik lösemi/ küçük lenfositik lenfomada (CLL/SLL) hızlı progresyon ve agresif gidişle ilişkileri belirlenen zeta associated protein-70 (ZAP-70) ve CD38 proteinleri ile apopitozisi indükleyen ve kötü prognostik indikatör olduğuna ilişkin kuşkular bulunan Fas ve bunun ligandı olan Fas ligand (FasL) arasındaki olası ilişkileri değerlendirmek ve bunların ekspresyonunun kemik iliği tutulum paternleri ile bağlantısı olup olmadığını ortaya koymak amacıyla planlanmıştır. Gereç ve Yöntem: Sekiz yıllık süre içinde kemik iliği biyopsisinde CLL/SLL tanısı konan ve tanıları akım sitometriyle doğrulanan 50 olgunun kemik iliği biyopsi materyallerinin parafin bloklarından elde edilen kesitlere avidin-biotin peroksidaz yöntemiyle ZAP-70, CD38, Fas ve FasL antikorları uygulanmıştır. Tümör hücrelerinin her bir antikorla boyanma oranları çift-kör semi-kantitatif bir yöntemle saptanarak birbirleriyle karşılaştırılmış; her bir antikor ise kendi içinde kemik iliği tutulum paternleri (diffüz, interstisiyel, noduler) açısından değerlendirilmiştir. Bulgular: Hızlı ilerleyen klinik özellikler ve erken tedavi gerektiren agresif seyirli hastalığın (lenfositoz, splenomegali, anemi, trombositopeni) belirleyicisi oldukları yaygın olarak kabul edilen ZAP-70 ve CD38’in tümör hücrelerince ekspresyonu açısından istatistiksel olarak anlamlı bir paralellik (P=0.002) bulunmuş; benzer bir paralellik bu iki belirleyici ile FasL arasında da saptanmıştır (sırasıyla P=0.023 ve P=0.021). Fas ekspresyonu ile diğer üç belirleyici arasında anlamlı bir ilişki kurulamamıştır. CLL/SLL kemik iliği tutulum paternleri açısından ise, ZAP-70 ekspresyonunun diffüz tutulumda interstisiyel ve noduler tutuluma göre istatistiksel olarak anlamlı biçimde fazla olduğu saptanmıştır (sırasıyla P=0.029 ve P=0.037). Diğer belirleyicilerle, kemik iliği tutulum paterni ile boyanma oranı arasında anlamlı bir ilişki görülmemiştir. Sonuç: CLL/SLL’de ZAP-70 ve CD38 ekpresyonlarının kötü prognostik belirleyiciler oldukları kabul edilmek kaydıyla, artmış FasL ekpresyonunun da ek bir negatif prognostik parametre olarak kullanılabileceği ve kemik iliğinde diffüz CLL/SLL infiltrasyonunun kötü prognoz belirtisi olarak dikkate alınmaya devam edilmesi gerektiği sonucuna varılmıştır.

RELATIONSHIP AND PROGNOSTIC VALUE OF ZAP-70, CD38 AND FAS/FAS LIGAND EXPRESSION WITH BONE MARROW UPTAKE PATTERNS IN CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA

Introduction: This study is planned to evaluate the possible relationship between zeta associated protein-70 (ZAP-70) and CD38 proteins, those which are concerned with rapid progression and agressive clinical course in chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL); and Fas and its ligand Fas ligand (FasL), which induct apoptosis and are suspected to be poor prognostic indicators in that tumor. Material and Methods: By avidine-biotin peroxidase method, ZAP-70, CD38, Fas and FasL antibodies were applied to sections obtained from paraffin blocks of bone marrow biopsy materials of 50 patients, who were diagnosed as CLL/SLL in 8-years time period and whose diagnoses were confirmed by flow cytometry. The ratio of stained tumor cells with each antibody were calculated by using a double-blind semi-quantitative method and compared with each other; and each antibody was evaluated according to bone marrow infiltration patterns of the tumor, i. e., diffuse, interstitial and nodular. Results: A statisticaly significant positive correlation (P=0.002) was found between expressions of ZAP-70 and CD38, which are widely accepted as predictors of rapidly progressing clinical features and aggresive disease requiring early treatment (lymphocytosis, splenomegaly, anemia, thrombocytopenia) and a similar correlation was obtained between these two markers and FasL (P=0.023 and P=0.021, respectively). No statistically significant results were established between Fas expression and the other three markers. In bone marrow CLL/SLL infiltration aspect, statistically significant more ZAP-70 expression is found in diffuse infiltration pattern in comparison to interstitial and nodular patterns (P=0.029 and P=0.037, respectively), confirming the negatif prognostic effect of diffuse infiltration. With other markers, no remarkable results were obtained between infiltration patterns and staining ratio. Conclusion: Since ZAP-70 and CD38 overexpressions are accepted as poor prognostic predictors in CLL/SLL, it is concluded that increased FasL expression can be used as an additional negative prognostic parameter. New studies with larger series are needed to confirm this conclusion.

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