Purpose To investigate the frequencies of p16 gene deletion,methylation and the loss of p16protein expression and to evaluate their clinicopathological implication in malignant lymphomas. Methodsrn Fifty fresh and 115 paraffin-fixed, formalin-embedded lymphoma tissue samples were studied. PCRamplification was employed to detect homozygous deletion of p16 gene while restriction enzyme-specific PCRtechnique was used to detect hypermethylation of p16 gene 5' CpG island. We also perfommedimmunohistochemical procedure to identify the expression of p16 protein. And 8 cases of reactive lymphoidhyperplasia were studied as negative control. Results The frequencies of p16 gene homozygous deletionand p16 gene methylation were 24.0% and 32.0%, respectively. The rates of the loss of p16 geneexpression were 46.0 %, 54.5 % and 31.6 % in B-NHL, T-NHL, and HL, respectively. The frequent p1 6gene inactivation was generally limited to those high-grade lymphoma subtypes. And no p16 abnommilitieswere observed in all of 9 RH cases. Conclusions p16 abnormality is a frequent event in malignantlymphoma, the abnormal p16 gene expression is involved in the tumorigenesis and progression of lymphoma.%目的 检测恶性淋巴瘤(ML)中p16基因的缺失、甲基化及p16蛋白的表达，探讨p16基因异常在淋巴瘤中的意义。方法 收集淋巴瘤新鲜组织标本50例，存档石蜡包埋组织标本115例，均包括T、B非霍奇金淋巴瘤(NHL)及霍奇金淋巴瘤(HL)。用PCR、甲基化特异的PCR方法检测新鲜组织中的p16基因的等位缺失及5’CpG岛异常甲基化；用免疫组织化学方法检测石蜡标本中p16蛋白的表达情况。另外，分别选取9例反应性增生(RH)组织的标本作对照。结果 12/50例(24.0％)新鲜标本中检出p16基因纯合性缺失，16/50例(32 0%)检出p16基因异常高甲基化；石蜡包埋标本中p16蛋白的失表达率为41.6％，其中B-NHL为46.0％，T-NHL为54.5%，HL为31.6％。恶性程度较高的淋巴瘤类型中p16蛋白的失表达率也相应较高，各类型之间比较：弥漫性大B细胞淋巴瘤(DLBCL)和滤泡性淋巴瘤(FL)的p16失表达率存在组间差异的显著性。所有RH标本均未见p16基因或蛋白表达的异常。结论 恶性淋巴瘤中p16基因的异常是一个频发事件，p16基因表达异常参与了淋巴瘤的发生及进展。
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