Non-Hodgkin Lenfoma`da Cyclin D1 ve Proliferating Cell Nuclear Antigen`in prognostik parametrelerle olan ilişkisi

Abstract

ÖZET Non-Hodgkin Lenfoma (NHL) lenfoid dokunun oldukça heterojen bir profil gösteren neoplazi grubudur. Histopatolojisi, immünolojisi ve moleküler genetiği ile ilgili halen pek çok bilinmeyen vardır. NHL'de tümörün proliferatif aktivitesini tayin etmek için hücre siklusunda kritik noktalarda görev yapan cyclinDl ve Proliferating Cell Nuclear Antigen (PCNA) kullanılabilecek önemli nükleer belirleyicilerdir. Bu çalışmada Çukurova Üniversitesi Tıp Fakültesi Onkoloji Bilim Dalı'nda tanı alan NHL'lı olgulardan 52'sine ait doku kesitlerine immunhistokimyasal yöntemle cyclinDl ve PCNA monoklonal antikoru uygulandı. CyclinDl monoklonal antikoru ile incelenen 40 olgunun yalnızca birinde nükleer cyclinDl pozitifliği bulundu. İki olgu zayıf nükleer ve sitoplazmik boyanma, bir olgu ise sadece sitoplazmik boyanma özelliği gösterdi. Literatür bilgileri ışığında yalnızca nükleer boyanma paterni gösteren olgu cyclinDl pozitif olarak yorumlandı. Olgunun klinik ve immunfenotipik özellikleri dikkate alınarak Mantle Hücreli Lenfoma (MCL) olabileceği düşünüldü. Serimizde %2.5 oranında saptanan nükleer cyclinDl pozitifliği, tüm NHL popülasyonu içindeki cyclinDl ekspresyon sıklığı ile uyumluydu. MCL dışında kalan genel lenfoma grubu içinde cyclinDl ekspresyonunun önemini kavramak için nükleer cyclinDl boyanmasının yanısıra sitoplazmik boyanmanın anlamı da aydınlatılmalı, daha fazla sayıda olguda, farklı yöntemlerle incelemeler yapılmalıdır. PCNA monoklonal antikoru ile incelenen 48 olguda PCNA boyanma yüzdesi arttıkça histolojik grade'in yükseldiği gözlendi. PCNA boyanma yüzdesi ile toplam takip süresi arasında ilişki bulunamaması olguların düzenli takip edilememiş olmalarıyla ve olgu sayısının azlığı ile açıklandı Serimizde immunhistokimyasal yöntemle cyclinDl ve PCNA boyanmasının NHL prognozundaki yeri, olgu sayımızın yeterli düzeyde olmaması ve hasta takiplerindeki hastalara ait aksamalar nedeniyle net olarak tayin edilememiştir. Prognoz üzerinde etkili olan klinik ve laboratuar parametrelerinin immunhistokimyasal yöntemlerle ve gerekirse daha komplike incelemelerle beraber çok geniş serilerde değerlendirilmesinin NHL'nm anlaşılabilmesi için gerekli olduğu sonucuna varılmıştır. Anahtar Kelime: Non-Hodgkin Lenfoma, CyclinDl, Proliferating Cell Nuclear Antigen, immunhistokimya IVTHE RELATIONSHIP OF CYCLIND1 AND PROLIFERATING CELL NUCLEAR ANTIGEN WITH OTHER PROGNOSTIC PARAMETRES IN NON- HODGKIN'S LYMPHOMA ABSTRACT Non-Hodgkin's Lymphoma is a malignant disorder of the lymphoid tissue which exhibits a heterogenous profile. There are many questions about its histopathology, immunology and molecular genetics. Proliferative activity of NHL can be detected by cyclinDl and Proliferating Cell Nuclear Antigen (PCNA) that are important nuclear markers acting at critical points in cell cycle. In this trial tissue samples of 52 patients with NHL diagnosed in Çukurova University, Department of Oncology were examined by cyclinDl and PCNA monoclonal antibodies immunohistochemically. Fourty of cases were stained with cyclinDl monoclonal antibody and only one presented nuclear cyclinDl positivity. Two cases exhibited faint nuclear and cytoplasmic positivity, while one case showed cytoplasmic positivity. Depending on the information in literature, we reported the case only with nuclear staining pattern as cyclinDl positive. Considering the clinical and immunophenotypical features, this case could probably be Mantle Cell Lymphoma (MCL). We detected nuclear cyclinDl positivity at a ratio of 2.5%. This ratio is compatible with frequency of cyclinDl expression in general NHL population. Further studies including more cases, using different methods and pointing out the meaning of cytoplasmic cyclinDl positivity are needed to evaluate the importance of cyclinDl expression in general NHL population in addition to MCL. Fourty-eight cases were stained with monoclonal PCNA antibody. The higher the PCNA staining percent, the higher the histological grade was found to be. No relation was detected between PCNA staining percent and total follow-up time. This was probably because of the incompliance of cases to regular clinical follow-up and limited number of cases being involved. In our study the importance of immunohistochemically detected cyclinDl and PCNA in NHL could not be clearly identified due to the limited number of cases involved and incomplete follow-up. We concluded that to answer the questions about NHL; clinical and laboratory parameters that affect the prognosis should be studied with irnmunohistochemical V

THE RELATIONSHIP OF CYCLIND1 AND PROLIFERATING CELL NUCLEAR ANTIGEN WITH OTHER PROGNOSTIC PARAMETRES IN NON- HODGKIN'S LYMPHOMA ABSTRACT Non-Hodgkin's Lymphoma is a malignant disorder of the lymphoid tissue which exhibits a heterogenous profile. There are many questions about its histopathology, immunology and molecular genetics. Proliferative activity of NHL can be detected by cyclinDl and Proliferating Cell Nuclear Antigen (PCNA) that are important nuclear markers acting at critical points in cell cycle. In this trial tissue samples of 52 patients with NHL diagnosed in Çukurova University, Department of Oncology were examined by cyclinDl and PCNA monoclonal antibodies immunohistochemically. Fourty of cases were stained with cyclinDl monoclonal antibody and only one presented nuclear cyclinDl positivity. Two cases exhibited faint nuclear and cytoplasmic positivity, while one case showed cytoplasmic positivity. Depending on the information in literature, we reported the case only with nuclear staining pattern as cyclinDl positive. Considering the clinical and immunophenotypical features, this case could probably be Mantle Cell Lymphoma (MCL). We detected nuclear cyclinDl positivity at a ratio of 2.5%. This ratio is compatible with frequency of cyclinDl expression in general NHL population. Further studies including more cases, using different methods and pointing out the meaning of cytoplasmic cyclinDl positivity are needed to evaluate the importance of cyclinDl expression in general NHL population in addition to MCL. Fourty-eight cases were stained with monoclonal PCNA antibody. The higher the PCNA staining percent, the higher the histological grade was found to be. No relation was detected between PCNA staining percent and total follow-up time. This was probably because of the incompliance of cases to regular clinical follow-up and limited number of cases being involved. In our study the importance of immunohistochemically detected cyclinDl and PCNA in NHL could not be clearly identified due to the limited number of cases involved and incomplete follow-up. We concluded that to answer the questions about NHL; clinical and laboratory parameters that affect the prognosis should be studied with irnmunohistochemical Vmethods, with further methods in larger populations. Key Words: Non-Hodgkin's Lymphoma, CyclinDl, Proliferating Cell Nuclear Antigen, Immunohistochemistry VI