滤泡性淋巴瘤与反应性淋巴滤泡增生的免疫组化及DNA图像分析研究

目的：观察滤泡性淋巴瘤（ＦＬ）与反应性淋巴滤泡增生（ＲＦＨ）中滤泡生发中心细胞（ＧＣＣｓ）核ＤＮＡ含量、倍体情况以及ｂｃｌ－２癌基因蛋白、免球蛋白轻链（ＩｇＬ）表达情况，探讨它们对于二都鉴别诊断的意义。方法：对２１例ＦＬ及２１例ＲＦＨ进行ｂｃｌ－２蛋白、Ｋｆｐｐａ、Ｌａｍｂｄａ轻链蛋白免疫组化检测及ＤＮＡ图像细胞分析。结果：６１．９％ＦＬ中ＧＣＣｓ有ｂｃｌ－２表达而ＲＦＨ的ＧＣＣｓ均为ｂｃｌ－２阴     

人脑胶质瘤中Bcl—2和p53癌基因蛋白的表达

应用免疫组化ＳＰ法观察４７例人脑胶质瘤中Ｂｃｌ－２和ｐ５３基因蛋白的表达。结果发现Ｂｃｌ－２蛋白阳性率为１４．９％（７／４７），ｐ５３蛋白的表达率为３６．２％（１７／４７），表达与肿瘤组织学分级和肿瘤复发有关。反应性胶质细胞增生和正常脑组织中ｂｃｌ－２和ｐ５３均为阴性。结果表明ｂｃｌ－２基因在脑胶质瘤发生过程中的作用有限；ｐ５３基因异常表达与胶质瘤的发生有关，且与肿瘤的恶性度和预后有关；Ｂｃｌ－２和ｐ５３两种癌基因蛋白表达无明显关系。     

非霍奇金淋巴瘤TCRδ基因不完全重排的研究

根据ＴＣＲδ基因的Ｖδ２和Ｄδ３、Ｊδ之间内含子序列设计两端引物，建立了ＴＣＲδ基因的Ｖδ２～Ｄδ３不完全重排半嵌套式ＰＣＲ检测方法，对５７例非霍奇金淋巴瘤（ＮＨＬ）进行分析，５２．６％获得阳性结果；而正常人外周血淋巴细胞、淋巴结反应性增生及淋巴结转移性癌均为阴性，在此基础上，又建立了ＰＣＲ－ＳＳＣＰ银染检测方法进行分析，阳性病例呈现一系列清晰条带，而阴性者呈现模糊涂片现象，ＰＣＲ－ＳＳＣＰ两种方法分析的结果一致，说明二者均可应用于ＴＣＲδ基因重排研究，区别淋巴系细胞的单克隆性或多克隆增生，确定肿瘤的克隆性，可以作为ＮＨＬ的一种基因标志用于淋巴瘤的诊断，并有助于分析淋巴细胞的分化情况。     

bcl-2、bcl-6在非霍奇金淋巴瘤中的表达及其与临床行为特征的相关性研究

ｔ(14;18)及ｔ(3:14) (ｑ2 7:ｑ32 )是Ｂ系淋巴瘤中最常见的两种染色体易位 ,分别为第 1位和第 3位 ,这两种易位导致了ｂｃｌ 2、ｂｃｌ 6原癌基因的激活 ,它们与Ｂ淋巴细胞的凋亡和分化有关 ,在其发育的不同阶段起作用。我们应用ＳＰ免疫组化方法检测了两种蛋白在非霍奇金淋巴瘤 (ＮＨＬ)中的表达 ,并探讨其与ＮＨＬ临床行为特征的相关性。一、材料与方法我院 1990～ 1998年收治的原发于淋巴结内ＮＨＬ中资料完整者 89例。男性 5 6例 ,女性 33例。Ⅰ～Ⅱ期 36例 ,Ⅲ～Ⅳ期 5 3例。弥漫大Ｂ细胞淋巴瘤 (ＤＬＢＣＬ) 37例 ,滤泡中心细胞型淋…     

ｐ５３、Ｂｃｌ ２、Ｂａｘ、Ｂｃｌ-ｘＬ和Ｂｃｌ-ｘＳ蛋白在胰腺癌中的表达

目的　探讨胰腺癌组织中ｐ５３和Ｂｃｌ-２家族（Ｂｃｌ-２、Ｂａｘ、Ｂｃｌ-ｘＬ、Ｂｃｌ-ｘＳ）蛋白的表达及其与细胞凋亡的关系。方法　免疫组化法检测３５例胰腺癌组织中ｐ５３蛋白表达,分为ｐ５３阴性表达组（１８例）和ｐ５３阳性表达组（１７例）;Ｗｅｓｔｅｒｎｂｌｏｔ法检测胰腺癌组织中ｐ５３、Ｂｃｌ-２、Ｂａｘ、Ｂｃｌ-ｘＬ和Ｂｃｌ-ｘＳ蛋白表达;ＴＵＮＥＬ法检测３５例胰腺癌组织中凋亡指数（ＡＩ）。结果 Ｂｃｌ-２蛋白在ｐ５３阳性表达组上调,而在ｐ５３阴性表达组下调（Ｐ＝０.０４７）;Ｂａｘ和Ｂｃｌ-ｘＬ蛋白在ｐ５３不同表达两组中都明显上调（Ｐ＝０.２７４,Ｐ＝０.３３４）;Ｂｃｌ-ｘＳ在ｐ５３阳性表达组明显下调,在ｐ５３阴性表达组明显上调（Ｐ＝０.０１）;在ｐ５３不同表达两组中,ＡＩ分别为１２.１±２.４７和９.１±１.４８（Ｐ＝０.０２３）;上述Ｂｃｌ-２家族各成员表达与ＡＩ无相关性（Ｐ＞０.０５）,而ｐ５３不同表达Ｂｃｌ-２／Ｂａｘ比值与ＡＩ有明显的相关性（Ｐ＜０.０１）。结论　Ｂｃｌ-２是依赖ｐ５３调节的抗凋亡蛋白,Ｂｃｌ-ｘＳ是依赖ｐ５３调节的促凋亡蛋白,而ｐ５３主要通过调节Ｂｃｌ ２／Ｂａｘ比值发挥凋亡调节作用。     

非霍奇金淋巴瘤中Cyclin D1和p34~(cdc2)蛋白的检测

为了研究非霍奇金淋巴瘤（ＮＨＬｓ）中细胞周期调节因子ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 蛋白表达与肿瘤分化程度和免疫分型的关系,对４０ 例ＮＨＬｓ 进行ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 蛋白免疫组化（ＳＰ法）染色。在４０ 例ＮＨＬｓ 中,有１９ 例（４７．５ ％）ＣｙｃｌｉｎＤ１ 阳性表达,２３ 例（５７．５ ％）ｐ３４ｃｄｃ２ 阳性表达。１０ 例淋巴结良性病变中６ 例生发中心细胞ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 弱阳性表达。低分化ＮＨＬｓ 的ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 阳性率明显高于高分化ＮＨＬｓ（Ｐ＜ ０．０５）,而同免疫分型无关（ Ｐ＞０ ．０５） 。２ 个细胞周期调节因子的表达具有高度一致性（Ｐ＜０ ．０５）。提示２ 个细胞周期调节因子参与ＮＨＬｓ 的发生发展过程,其阳性表达率及表达强度同ＮＨＬｓ 恶性程度有密切关系,而同免疫分型无明显联系。ＣｙｃｌｉｎＤ１ 和ｐ３４ｃｄｃ２ 蛋白在部分ＮＨＬｓ 中共同起作用,使Ｇ１ →Ｓ期和Ｇ２ →Ｍ 期２ 个细胞检查点控制减弱。     

癌基因Bcl—2蛋白在肺癌组织中的表达

目的：探讨癌基因蛋白Ｂｃｌ－２在肺癌组织中的表达及意义。方法：采用鼠抗人Ｂｃｌ－２蛋白单克隆抗体，应用免疫组化方法检测肺癌组织抗凋亡基因Ｂｃｌ－２的表达产物。结果：６９例肺癌Ｂｃｌ－２阳性率为３０．４％，其中鳞癌３３．３％（９／２７），腺癌１４．８％（４／２７），大细胞癌０（０／２），小细胞癌６１．５％（８／１３）。小细胞肺癌阳性率明显高于非小细胞肺癌（ｐ〈０．０５），Ｂｃｌ－２表达与肿瘤大小、Ｔ     

肺癌中凋亡抑制基因bcl—2蛋白产物表达的研究

应用即用型ＳＡＢＣ免疫组化方法观察凋亡抑制基因ｂｃｌ－２蛋白在６３例肺癌组织中的表达情况以探讨该基因与肺癌发生、发展的关系。结果表明，ｂｃｌ－２蛋白在肺癌有较高表达（５０．８％）；在鳞癌和腺癌中ｂｃｌ－２蛋白和阳性率随着分化程度的降低而下降，高分化与低分化鳞癌、腺癌间ｂｃｌ－２阳性率的差异有显著性（Ｐ〈０．０５）；ｂｃｌ－２阳性率的差异有显著性（Ｐ〈０．０５）；ｂｃｌ－２蛋白表达与肿瘤临床病理分期     

Bcl-2基因重排在恶性淋巴瘤微小残留病变检测中的应用

目的建立敏感的检测淋巴瘤微小残留病变（ＭＲＤ）的方法,探索Ｂｃｌ２基因重排在恶性淋巴瘤的分期、化疗疗效和预后评估中的意义。方法多聚酶链反应（ＰＣＲ）检测Ｂｃｌ２／ＪＨ基因重排,系列稀释试验检测该方法的敏感性。结果９种恶性淋巴瘤细胞系中,ＳｕＤＨＬ４,ＳｕＤＨＬ６有Ｂｃｌ２／ＪＨ基因重排,系列稀释试验检测该方法的敏感度达１∶１０５。滤泡性淋巴瘤（ＦＮＨＬ）患者１６例中,４例外周血和骨髓中同时检出Ｂｃｌ２（ＭＢＲ）／ＪＨ基因重排,化疗达ＣＲ后仍存在。结论多聚酶链反应检测Ｂｃｌ２／ＪＨ基因重排,是检测滤泡性淋巴瘤患者微小残留病变的一个快速、有效、敏感的方法,对疾病的分期、疗效和预后评估有一定的临床应用价值。     

肺癌组织中bcl—2和Bax的表达

目的　探讨凋亡相关基因ｂｃｌ－２ 基因和Ｂａｘ 基因在肺癌中的表达。方法　应用原位杂交技术检测了３８ 例肺癌组织及２１例肺部良性组织ｂｃｌ－２ ｍ ＲＮＡ表达情况;应用免疫组织化学法对Ｂａｘ 蛋白进行检测。结果　肺癌组织ｂｃｌ－２基因、Ｂａｘ 蛋白的表达（４２．１％ 、３４．２％ ）明显高于肺部良性组织（４．８％ 、０）Ｐ＜ ０．０１。结论　ｂｃｌ－２、Ｂａｘ蛋白在肺癌中的表达率较高,ｂｃｌ－２、Ｂａｘ 可能会成为肺癌的重要分子标志物。     

Lectin histochemistry of malignant tumors. I. Peanut agglutinin (PNA) receptors in follicular lymphoma and follicular hyperplasia: an immunohistochemical study

Peanut agglutinin (PNA) receptors were studied in 37 cases of reactive follicular hyperplasia and 66 follicular lymphomas, using the unlabeled peroxidase-antiperoxidase (PAP) method on paraffin embedded material. Based on the binding sites of the lectin, positively stained cells were easily recognized as either cytoplasmic receptor-positive (CR+) or surface receptor-positive (SR+) cells. In the lymph node specimens, CR+ cells corresponded to macrophage-histiocytes and possibly dendritic reticulum cells; SR+ cells corresponded to lymphoid cells. Three categories of CR+ cells were noted: large, medium, and small. The large CR+ cells were present in most germinal centers from reactive nodes, but were virtually absent in neoplastic follicles. Varying numbers of medium and small CR+ cells were seen in reactive as well as neoplastic follicles. SR+ cells were present in both follicular lymphoma (64%) and follicular hyperplasia (19%). In neoplastic follicles, SR+ cells were distributed uniformly throughout every follicle in the node revealing no relation to the orientation of the node. In reactive follicles, however, the occurrence of SR+ cells was not only infrequent, but also focal, and was often associated with the polarity of the follicles. The uniform distribution of SR+ tumor cells produced a characteristic staining pattern of neoplastic follicles which, along with the disappearance of the large CR+ cells, would provide an additional feature useful in the differential diagnosis of neoplastic from reactive follicles.     

Differential expression of cytokines, chemokines and their receptors in follicular lymphoma and reactive follicular hyperplasia: assessment by complementary DNA microarray

Follicular lymphoma (FL) is pathologically categorised as a low-grade B-cell lymphoma and histopathologically shows follicular proliferation of neoplastic B cells. In the neoplastic follicles of FL, the presence of T cells, macrophages and follicular dendritic cells (FDCs) suggests that these cells may promote a favourable environment for the growth of FL cells. Because FL cells are generally associated with FDCs, FDCs may be considered an important source of cytokines and chemokines. FDCs form the framework for germinal centres and also provide networks for nodules of FL. To evaluate the gene expression in neoplastic follicles of FL and reactive follicles of reactive follicular hyperplasia (RFH), we performed gene expression profiling of FL (n=5) and RFH (n=5) using complementary DNA (cDNA) microarray of cytokines/chemokines and their receptors. FL and RFH exhibited a diffuse down-regulated profile compared with normal peripheral blood cells, which were used as controls, although some genes displayed up-regulated profiles. Hierarchical clustering analysis separated FL and RFH into two distinct groups based on their gene expression profiles. FL cases exhibited significantly higher expression of interleukin 3 receptor alpha (IL-3Ralpha) than RFH. Immunohistochemically, neoplastic follicles of FL frequently expressed IL-3Ralpha, especially in FDCs, but not in FL cells. However, IL-3Ralpha expression was rare or weak in the reactive follicles of RFH. These findings suggest the importance of the micro-environment for FL cell growth. Further studies of cDNA microarray should provide new insight into the molecular pathology of FL and may allow the design of improved therapies.     

HNK-1+ cells in non-Hodgkin's lymphoma: lack of relation with transferrin receptor expression on malignant cells

It has been proposed that Natural Killer (NK) cell activity is involved in host defence against neoplasia, and that NK cells react with or recognize the transferrin receptor (TrR) on target cells. HNK-1 expression has been related to NK cell function. Therefore, in 118 cases of non-Hodgkin's lymphoma (NHL) we studied the occurrence and distribution of HNK-1+ cells by immunohistochemistry, and simultaneously assessed the expression of TrR on malignant cells. In NHL of intermediate or high grade malignancy there was uniform expression of TrR on malignant cells. In low grade malignancy NHL, only lymphocytic and lymphoplasmacytoid lymphomas were TrR negative, except for faint staining of proliferation centres. In 23 cases of follicular lymphoma, 9 showed the absence of HNK-1+ cells in neoplastic follicles. In 16/23 cases HNK-1+ cells were present around follicles or in interfollicular areas: 8 of these cases revealed a higher density of HNK-1+ cells at this site than inside the follicles. In 22/26 cases with high grade malignancy NHL, HNK-1+ cells were absent or present in small density, which is different from the presence in higher density in low grade malignancy NHL. We conclude that (i) TrR expression on NHL cells is not obligatory related with histological class or malignancy grade of the tumour, and that (ii) HNK-1+ cells are not universally present in areas of malignant cells, in particular in follicular lymphoma and in NHL of high grade malignancy.     

Follicular lymphoma with prominent sclerosis (“sclerosing variant of follicular lymphoma”) exhibiting a mesenteric bulky mass resembling inflammatory pseudotumor. Report of three cases

We present three cases of follicular lymphoma (FL) exhibiting prominent sclerosis (sclerosing variant of follicular lymphoma), resembling inflammatory pseudotumor (IPT) of the lymph node, arising from mesenteric lymph node. Clinically all three cases represented bulky masses of the mesenteric lymph node. Histologically, the lesions were characterized by neoplastic lymphoid follicles separated by stromal collagenization and sclerotic process, with cellular infiltrate extending into the adjacent adipose tissue. The lesions contained variable cellular spindle cell proliferation and inflammatory infiltrate including numerous reactive T cells and histiocytes. Small capillary proliferation with vascular change was also noted. Immunohistochemical study demonstrated the myofibroblastic nature of the spindle cells. Moreover, neoplastic follicles were composed of intermediate to medium-sized lymphocytes, somewhat resembling reactive lymphoid aggregates. The overall histomorphological findings of the three lesions were similar to those of IPT of the lymph node. However, CD10, Bcl-2 and Bcl-6 immunostaining demonstrated the neoplastic nature of the lymphoid follicles and the lesions were diagnosed as FL grade 1. The present three cases indicate that the sclerosing variant of grade 1 FL should be added to the differential diagnosis from IPT of the lymph node.     

Immunohistochemical differentiation of follicular lymphoma from florid reactive follicular hyperplasia with monoclonal antibodies reactive on paraffin sections

In this study monoclonal antibodies which recognize lymphoid-associated antigens on paraffin sections (LN1, MB2, L26, MT2, UCHL1) have been evaluated to assess their usefulness in the distinction between reactive and neoplastic lesions of lymphoid follicles. Thirty-three follicular lymphoma samples and 36 reactive samples (lymph nodes and tonsils) were analyzed. MT2 appeared as the most valuable immunophenotypic marker as emerged from a comprehensive quantitative evaluation of 2329 reactive follicles and 2288 neoplastic follicles performed on MT2 immunostained sections. MT2-positive follicles were found in all lymphoma samples but one. Overall 1908 of 2288 neoplastic follicles were judged as positive whereas no follicles with comparable strong MT2 immunoreactivity could be found in non neoplastic samples. These latter showed weak MT2 positivity only in about 10% (224/2329) of reactive follicles. This study confirms that MT2 follicular positivity can be considered a reliable marker of follicular neoplasia, although negative results ought to be considered with caution. The detection of centrofollicular cells outside the germinal centers, which is considered a reliable criterion of follicular neoplasia, was highly improved by LN1 immunostaining. On the other hand pan-B antibodies such as L26 and MB2 were less informative because of the large number of B-lymphocytes observed in interfollicular areas of nonneoplastic samples.     

Quantitative analysis detects ubiquitous expression of apoptotic regulators in B cell non-Hodgkin's lymphomas.

To determine whether the expression levels of Bcl-2 family apoptotic regulators are correlated with the histopathological heterogeneity of B cell non-Hodgkin's lymphomas (NHL), we quantified their expression in malignant B cell populations isolated from 33 biopsy samples, including small lymphocytic lymphoma (SLL, n = 9), mantle cell lymphoma (MCL, n = 8), follicular lymphoma (FL, n = 8), and diffuse large cell lymphoma (DLCL, n = 8). Normal B cells purified from reactive lymph nodes and tonsil (n = 3) were used as controls. Cell lysates were analyzed by Western blotting, and signals quantified by densitometry. Expression of Bcl-2 and its homologues, Bcl-xL, Bcl-xS, Bax, Bad, Bak and Bag-1, was detected in all NHL cases, with wide variations between histological subtypes and within each subtype. Statistically significant differences were: (1) a higher level of Bad expression in DLCL compared to FL and MCL; (2) a lower level of Bak expression in FL compared to DLCL, SLL and MCL; and (3) a higher Bag-1 expression level in FL compared to SLL. When compared to NHL cells, normal B cells showed a higher level of Bax expression, and a lower level of Bcl-xL expression. Thus, quantitative analysis shows ubiquitous expression of Bcl-2 family proteins in normal and neoplastic B cells; the variations in expression levels may contribute to both the B-NHL clinicopathological diversity and the different apoptotic sensitivities of normal B cells vs B-NHL cells.     

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of alpha V beta 3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in alpha V beta 3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of alpha V beta 3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.     

The expression of the peripheral cannabinoid receptor on cells of the immune system and non-Hodgkin's lymphomas

The peripheral cannabinoid receptor CB2 is expressed highly on normal human B-lymphocytes. C-terminal specific anti-CB2 antibody recognises a non-phosphorylated inactive receptor on na?ve and resting B-lymphocytes. Another, N-terminal specific CB2 antibody, primarily recognises B-cells present in the germinal centres of secondary follicles in lymph nodes. We hypothesise that N-terminal specific CB2 antibody recognises activated CB2 receptors. In this study, we showed using these antibodies, that expression of CB2 is generally absent on T-lymphocytes in reactive, non-malignant human lymphoid tissues. Applying single and dual immunohistochemistry, CD23(+) follicular dendritic cells and a small but significant subpopulation of CD68(+) macrophages showed positive staining with the N-terminal specific CB2 antibody but not with the C-terminal specific CB2 antibody. This may indicate the presence of an active CB2 receptor on these cells with possible involvement in immunomodulation. In contrast to the low expression on normal T-cells, abundant levels of CB2 protein were present on T-non-Hodgkin's lymphomas (NHL). Moreover, in many B-NHL, high CB2 protein expression was found as well. In contrast to the distinct expression patterns in normal immune tissues using the two different CB2 antibodies, NHL specimens in general stained positively with both. We conclude that CB2 receptor expression pattern may be abnormal in NHL.     

Complement receptor subtypes C3b and C3d in lymphatic tissue and follicular lymphoma

To substantiate the origin of follicular (nodular) lymphoma cells from germinal-centre cells, the lymphoma cells from 7 patients with follicular lymphoma and from 9 tonsils and 2 lymph nodes were studied for the presence and distribution of complement-receptor subtypes (i.e., the receptors for C3b and C3d). It was found that erythrocytes coated with antibodies and C3d (EAC3d) adhered exclusively to germinal centres, whereas erythrocytes coated with antibodies and C3b (EAC3b) adhered to germinal centres and in many instances to the regions between them. These findings indicate that germinal-centre cells bear both complement-receptor subtypes and that the B cells of the interfollicular area, which belong at least in part to the precursors of plasma cells, bear only a receptor for C3b. In frozen sections of follicular lymphomas, a similar distribution of complement-receptor subtypes was observed; EAC3d was bound exclusively to the neoplastic nodules, and EAC3b adhered to the neoplastic nodules and adjacent paranodular tissue. Receptor studies on suspended cells of both normal tonsils and follicular lymphomas revealed a slight predominance of EAC3d⁺ cells or equal numbers of EAC3b⁺ and EAC3d⁺ cells. The complete congruence in the expression and distribution of complement-receptor subtypes between tissues from follicular lymphomas and those from normal and hyperplastic tonsils or lymph nodes suggests that follicular lymphoma represents the neoplastic counterpart of the reactive germinal centre.     

92例非霍奇金淋巴瘤组织中Skp2和p27kip1蛋白的表达及相互关系

目的探讨92例非霍奇金淋巴瘤（NHL）组织中Skp2和p27^kip1蛋白的表达及相互关系。方法采用免疫组织化学方法检测92例NHL和14例反应性增生淋巴结组织中Skp2、p27^kip1蛋白及细胞增殖指标Ki-67的表达情况,结合病理资料进行统计分析;采用Western blot技术检测4种淋巴瘤细胞株内Skp2和p27^kip1蛋白的表达情况。结果Skp2蛋白在NHL组织中的表达高于反应性增生的淋巴结（不含生发中心）,且与增殖活性（Ki-67 LI）呈正相关,并随着肿瘤侵袭性增加而表达增高;p27^kip1蛋白在NHL组织中的表达低于反应性增生淋巴结（不含生发中心）,且与增殖活性呈负相关,并随着肿瘤侵袭性增加而表达减低;Skp2和p27^kip1蛋白在NHL组织中的表达无明显相关性。结论在NHL组织中,Skp2的高表达和p27^kip1的低表达均可能与NHL的发生发展有关。