div dir="ltr">Abstract:
Chronic lymphocytic leukemia (CLL) is a low-grade B-lineage lymphoid malignancy. It has a variable clinical course with a median survival ranging from two to twenty years and several biological markers were used to assess the disease activity. Ki-67 is a large nuclear protein associated with cell proliferation. It is an excellent marker used to measure the rate of tumor growth.The level of Ki-67 expression in advanced stage of CLL is higher than that in early stage .The antiapoptotic protein Bcl-2 is associated with dysregulation of the intrinsic apoptotic pathway. A number of studies revealed that high expression of the proto-oncogene Bcl-2 correlated with poor prognosis or resistance to chemotherapy in many tumours.
Aims of the study: 1-To evaluate the immunohistochemical expression of Ki67 and Bcl2 in chronic lymphocytic leukemia and to relate them with clinicopathological parameters including the Modified Rai staging system and pattern of bone marrow involvement. 2-To find any relation between the antiapoptotic marker Bcl2 and the proliferative marker Ki67 in CLL. Patients,materials and methods: This retrospective study was conducted on fifty formaline fixed paraffin embedded blocks of CLL cases ; their age range was 39-75 years along with twenty control cases with benign reactive marrow , from November 2009 to May 2010.
The sections of bone marrow biopsies were processed routinely and stained with H&E and immunohistochemical stain for Bcl2 and Ki67 and examined by Light Microscope.The immunostain Bcl2 was classified according to the scoring system used by Soini Y,et al. ,whereas the evaluation of the ki67 was sbased on the estimation of the percentage of positively stained nuclei as was used by Diop S,et al.
Results: This study revealed that there was significant correlation between ki-67 score and the clinical stage of the disease using Modified Rai system (P= 0.042). Moreover there was significant inverse correlation between Ki67 score with Hb concentration (p=0.003) and platelet count (p=0.039) ,whereas no significant correlation between ki-67 score and white blood cell count or lymphocyte % in the Bone Marrow and peripheral blood. Current study showed that there was no significant correlation between Bcl2 and the clinical stage of the disease using Modified Rai system or with any of the hematological parameters.
Furthermore , there was no significant correlation between Ki67 and Bcl2 markers. Conclusions: ● The proliferative marker Ki-67 expression was closely related to the clinical stage of the patient , thus it can be considered as informative and simple tool for assessing disease activity. ●This study revealed that Bcl2 expression in CLL is not related to the clinical stage of the patient , thus Bcl-2 mediated inhibition of poptosis is not a key factor in the pathogenesis of CLL. ● No correlation was found between Ki67 and Bcl2 score as they act on different pathways since ki67 is a proliferative and Bcl2 is an antiapoptotic marker.