【作者】 郭英；

【导师】 黄高昇；

【作者基本信息】 第四军医大学 ， 病理学与病理生理学， 2005， 博士

【摘要】 滤泡性淋巴瘤是最常见的低度恶性淋巴瘤,在形态上根据最新世界卫生组织制定的标准可以分为1级、2级、3级a和3级b~1。Bcl2,Bcl6和CD10是滤泡性淋巴瘤的免疫学标志,Bcl2(14;18)易位及Bcl6(3q27)易位是常见基因异常。但是迄今为止还没有大宗病例研究以综合分析其形态分类、免疫表型、基因异常以及它们之间的相互关系。Bcl2表达是滤泡性淋巴瘤的一项重要标志,是区分淋巴滤泡增生过长和滤泡性淋巴瘤的主要指标。主要由Bcl2基因易位导致的Bcl2高表达致使淋巴细胞凋亡障碍,在此过程中具有该易位的淋巴细胞有机会获得其他遗传学异常,最终导致滤泡性淋巴瘤的形成。这是滤泡性淋巴瘤发病机制的经典理论。然而并非所有的滤泡性淋巴瘤均表达Bcl2,约有10%-15%的滤泡性淋巴瘤缺乏Bcl2的表达。这类滤泡性淋巴瘤的发病机制未明。我们对261例滤泡性淋巴瘤进行了形态学分级、免疫表型测定及基因异常测定,以期了解滤泡性淋巴瘤组织学分级、免疫表型和基因异常的分布状况以及这些特征之间的相互关系。我们通过检测在Bcl2阴性、阳性滤泡性淋巴瘤中癌基因BclX,Bax,Bcl6和p53的表达情况来预测Bcl2阴性滤泡性淋巴瘤中可能替代Bcl2发挥抗凋亡作用的蛋白;并通过检测Bcl2和Bcl6易位来比较Bcl2表达阴性或阳性滤泡性淋巴瘤的遗传学异常以期发现Bcl2阴性、阳性滤泡性淋巴瘤更多还原

【Abstract】 Follicular lymphoma （FL） is the most frequently happened low grade lymphoma. Morphologically it can be devided into grade 1, 2, 3a and 3b subtype according to the lastest World Health Organization （WHO） criterion¹. Bcl2, Bcl6 and CD 10 are phenotypic markers of FL while Bcl2 translocation t（14;18） and Bcl6 translocation t（3q27） are recurrent gene aberrances of it¹. But so far there is no integrate study of morphology, immunophenotype and gene aberrances and their correlations from a large cohort of FL cases. We have detected histological grades, immunophenotype and gene aberrances from 261 cases of FL. We want to know the distribution of above items in whole FLs and the relationship of these characters. Bcl2 expression is the hallmark of FL and it is the main point to differentiate FL from follicular hyperplasia （FH） in usual diagnosis. The deregulated expression of Bcl2 mainly resulted from Bcl2 translocation can prevent apoptosis of lymphocytes and thus offer opportunities to gain other gene aberrances. Finally follicular lymphoma comes into being². Such theory is classical theory to explain the pathogenesis of follicular lymphoma. But not all FLs express Bcl2. There are about 10% -15% FLs lack such expression^3,4 and there is no mature theory to explain thelymphomagenesis of such kind of FL. In our present study we detected the expression of Bcl2 family proteins, Bcl6 and p53 and sought to find prosurvival proteins that can substitute the function of Bcl2. We detected the recurrent gene aberrances Bcl2 and Bcl6 translocation in order to know if the pathogenesis of these two kind of FL is different.The experiments and main results are as follows:1.We graded 261 cases of FL and got the histological grade distribution in Japanese FL as: Grade 1:26%, grade 2: 48%, grade 3a: 17%, grade 3b: 9%;We used immunostaining technique to detect the expression of Bcl2, Bcl6 and CD 10 in follicular lymphoma. We detected gene aberrances of FLs. To make analysis of phenotype and gene aberrances we selected 147 cases with full and definite data of immunostaining and fluorescence in situ hybridization （FISH）. The positivity of Bcl2 and CD10 is 91% and 80% respectively. It was significantly higher in low grade （grade 1 and 2） lymphoma and lower in high grade （grade 3a and 3b） lymphoma （p<0.001）. We found the immunostaining pattern of Bcl6 is different from follicular hyperplasia and FL. In FH, the staining intensity of Bcl6 is uniform and covers whole area of the follicle. But in FL the staining intensity is from weak to strong from case to case. Even in the same case the staining intensity of the positive cells is various. The positivity of Bcl6 is 71% and there was no significant difference between low and high grade FLs. We used FISH to detect t （14; 18） and t （3q27） in FL. The positivity of t （14; 18） is 81% from 147 cases studied. The positivity in grade 1 and 2 FL is 100% and 92% whereas the positivity is 44% and 43% in grade 3a and 3b cases. There is significant difference between low and high grade FLs （p<0.001）. The positivity of t （3q27） is 10%. It mainly occurred in high grade FLs. 32% grade 3a cases and 36% grade 3b carried this translocation.2. We selected two groups of FL with and without Bcl2 expression respectively with same component of histological grade cases. We detected proliferation and更多还原