非霍奇金淋巴瘤与p53蛋白表达的关系

目的 :探讨非霍奇金淋巴瘤 (NHL)与 p5 3蛋白表达的关系。 方法 :用免疫组化S P法检测 10 2例 (低度恶性 2 3例 ,中度恶性 36例 ,高度恶性 4 3例 )NHLp5 3蛋白表达 ,根据 p5 3蛋白阳性细胞百分率将其表达水平分为 4级 :0级 (阴性 ) ,1级 (1%～ 2 5 % ) ,2级 (2 6 %～ 5 0 % ) ,3级 (>5 0 % )。结果 :低度恶性组 2 0 / 2 3(87% )p5 3表达为 0级 ,中度恶性组 31/ 36 (86 1% )表达为 1级 ,高度恶性组 33/ 4 3(76 7% )表达为 2～ 3级。 2 5例随访 7～ 6 8个月 ,p5 30～ 1级NHL完全缓解率 (CRR ,11/ 14 )高于p5 32～ 3级NHLCRR (1/ 11,P <0 0 1) ,前者生存率 (13/ 14 )高于后者 (3/ 11,P <0 0 1)。NHLp5 3蛋白表达水平与其恶性度密切相关 (P <0 0 1)。结论 :p5 3蛋白表达阳性细胞百分率是判断NHL恶性度、疗效及预后较可靠的参数。肿瘤性p5 3蛋白表达检测对中高度恶性NHL的诊断有参考价值     

非霍奇金淋巴瘤EB病毒特异DNA序列的检测

目的　探讨EB病毒 (EBV)与中国南方地区非霍奇金淋巴瘤 (NHL)的相关性 ,以及EBV与不同类型NHL的关系。方法　采用PCR技术 ,检测 2 0 6例石蜡包埋的NHL组织及 2 3例反应性增生的淋巴组织中的EBV特异DNA序列。结果　(1 ) 2 0 6例NHL组织中 ,94例PCR扩增出EBV特异的DNA序列 ,阳性率 4 5 6 % ;对照组反应性增生的淋巴组织 2 3例中 ,5例阳性 ,阳性率 2 1 7% ;两者差异有显著性 (P <0 0 5 )。 (2 ) 2 0 6例NHL中B NHL 1 2 8例 ,EBV阳性者 4 8例 ,阳性率 37 5 % ;T NHL 78例 ,EBV阳性者 4 6例 ,阳性率 5 9 0 %。两者差异有显著性 (P <0 0 5 )。结论　EBV与中国南方地区NHL ,特别是T NHL有一定的相关性     

心脏原发性非霍奇金淋巴瘤1例

患者男 ,5 6岁。因恶心、呕吐、纳差、腹胀 1月余 ,加重 5天 ,心脏彩超显示“右房黏液瘤”入院。体检 :心率 118次 /ｍｉｎ ,ＢＰ 13 2 9/ 9 6ｋＰａ,颈静脉怒张 ,心音低钝 ,心律不齐 ,各瓣膜区未闻及病理性杂音。入院诊断 :右房黏液瘤。相关检查 :胸部Ｘ线及ＣＴ未见纵隔占位 ,同位素骨扫描及Ｘ线等未见异常改变 ,骨髓分析检查为正常骨髓象 ,血象 :ＷＢＣ 6 0× 10 9/Ｌ ,ＲＢＣ 4 5× 10 12 /Ｌ ,Ｈｂ 12 5 ｇ/Ｌ ,Ｐｌｔ 2 2 5× 10 9/Ｌ。于 2 0 0 0年 8月 16日行心脏肿瘤切除术 ,术中见肿瘤几乎占满右房腔 ,下腔静脉仅 1/ 3(后壁 )未…     

肠道原发性非霍奇金淋巴瘤32例的临床与病理学分析

目的研究肠道原发性非霍奇金淋巴瘤(NHL)的临床表现、病理特点及预后因素。方法复习32例肠道原发性NHL的临床资料、大体标本、HE切片及免疫组织化学染色结果,按2001年WHO淋巴造血系统肿瘤的标准重新进行分类。结果B细胞性NHL 21例,其中弥漫大B型15例,套细胞型2例,滤泡型1例,Burkitt淋巴瘤1例,黏膜相关淋巴组织淋巴瘤2例。T细胞NHL 10例(其中肠病相关型NHL2例和非肠病相关型NHL8例),组织细胞NHL1例。诊断时,9例为Ⅰ～Ⅱ期,23例为Ⅲ～Ⅳ期。随访4—168个月,死亡15例。B细胞NHL死亡率为7／21例(33％),T细胞NHL的死亡率为8／10。Ⅱ期死亡2例,均为T细胞NHL。Ⅲ-Ⅳ期死亡13例,占死亡数的86．6％。Cox多因素分析显示,最重要的预后因素是肿瘤的分期及肿瘤类型(分期P=0．002、肿瘤类型P=0．032)。结论肠道原发性NHL以弥漫大B型最多见。以结肠最多见,其次为小肠和回盲部,直肠最少。就诊时65．6％为Ⅲ-Ⅳ期患者。比较同期T、B细胞NHL,T细胞NHL预后差,死亡率高。分期越高预后越差,黏膜相关淋巴组织淋巴瘤等恶性度较低的淋巴瘤预后较好。     

心脏非霍奇金淋巴瘤1例

患者,男性,58岁,因咳嗽、咯痰2个月,心悸1周入院。体检:BP:15/11 kPa,双下肺可闻及湿罗音,心界向左下扩大,各瓣膜听诊区未闻及杂音。血常规示:Hb 130 g/L,RBC3·83×1012/L,WBC 6·9×109/L。ESR>82 mm/1 h。超声心动图示:(1)右室壁心包脏层占位性病变可能性大,(2)心包积液。心电图示:窦性心律,广泛性心肌缺血,低电压。胸部X片:(1)心包积液,(2)轻度肺淤血,(3)左膈面上稍高密度影,考虑为心包脂肪或胸膜增厚。CT示:心包积液,纵隔内有增大的淋巴结数个(可能为积液所致)。心包液结核抗体呈强阳性。临床考虑为:(1)肿瘤性心包炎,(2)结核性…     

原发性肾上腺非霍奇金淋巴瘤3例并文献复习

目的探讨原发性肾上腺恶性淋巴瘤的临床病理特征。方法对3例原发性肾上腺恶性淋巴瘤进行临床、病理组织学和免疫组织化学观察,并结合文献探讨其临床表现、病理形态及鉴别诊断。结果本病临床上无特异性,组织学上瘤细胞呈弥漫片状分布,细胞体积较大,多呈圆形或卵圆形,核仁明显,核深染,异型性明显,核分裂象易见。免疫表型：瘤细胞CD45、CD20、CD79α阳性,CD3、CK、S-100蛋白、CEA、Syn及CgA阴性。结论原发性肾上腺恶性淋巴瘤是一种罕见的恶性度较高的肿瘤,预后差。病理诊断上应与继发性肾上腺恶性淋巴瘤鉴别。     

儿童非霍奇金淋巴瘤64例临床病理分析

非霍奇金淋巴瘤(non-Hodgkin’s lymphoma，NHL)是儿童的一种常见病、多发病，严重威胁着儿童的生命。据不完全统计，其发病率居小儿实体瘤的前2位，占小儿恶性肿瘤的5％～7％；多在半年内死亡。因此，根据新的WHO分类，总结和分析儿童NHL的资料，将有助于提高对儿童NHL诊治水平。     

小脑原发性非霍奇金淋巴瘤一例

患者男 ,5 6岁。于 2 0 0 1年 5月初无明显诱因 ,出现眩晕 ,无其他功能障碍和胃肠道反映 ,尚不影响生活及劳动。 5月中旬开始在当地医院静点甘露醇及维脑路通治疗无效 ,后病情逐渐加重 ,偶有恶心及呕吐 ,遂转入我院就诊 ,实验室检查正常 ,Ｘ线胸片未见异常 ,头颅ＣＴ平扫未见异常 ,2 0 0 1年6月 12日行ＭＲＩ检查 ,回报结果 :小脑蚓部长Ｔ1,短Ｔ2病变 ,考虑肿瘤可能性大。于当天遂收住院治疗 ,此时已不能正常生活及工作。专科检查 :躯体感觉正常 ,四肢肌力Ⅴ级 ,肌张力适中 ,双侧肱二、三头肌肌腱及膝、跟腱反射减弱 ,双侧Ｈｏｆｆｍａｎｎ…     

原发性中枢神经系统非霍奇金淋巴瘤临床分析

目的：探讨原发性中枢神经系统非霍奇金淋巴瘤(primary central nervous system non-Hodgkin’s lymphoma,PCNSL)的临床特征、治疗及预后。方法：回顾性分析4例原发性中枢神经系统淋巴瘤的临床资料和治疗疗效观察,并随访患者的复发率及生存情况。结果：4例原发性中枢神经系统淋巴瘤患者均为男性,发病年龄46~76岁,中位58.75岁。病灶分别位于脑干双侧丘脑低节、右侧脑室、右侧枕叶、右侧小脑,以头痛引起的颅内高压为主要临床症状。4例患者均术后给予大剂量MTX(HD-MTX)为主的化疗+全脑放疗;随访3年,1例复发术后死亡,3例存活。结论：原发性中枢神经系统淋巴瘤多发于中老年男性,颅内高压为主要临床症状,B细胞亚型占绝对优势。HD-MTX联合全脑放射治疗原发性中枢神经系统淋巴瘤有效可行,可提高患者的远期生存率。     

Quasimonomorphic mononucleotide repeats for high-level microsatellite instability analysis

Microsatellite instability (MSI) analysis is becoming more and more important to detect sporadic primary tumors of the MSI phenotype as well as in helping to determine Hereditary Non-Polyposis Colorectal Cancer (HNPCC) cases. After some years of conflicting data due to the absence of consensus markers for the MSI phenotype, a meeting held in Bethesda to clarify the situation proposed a set of 5 microsatellites (2 mononucleotide repeats and 3 dinucleotide repeats) to determine MSI tumors. A second Bethesda consensus meeting was held at the end of 2002. It was discussed here that the 1998 microsatellite panel could underestimate high-level MSI tumors and overestimate low-level MSI tumors. Amongst the suggested changes was the exclusive use of mononucleotide repeats in place of dinucleotide repeats. We have already proposed a pentaplex MSI screening test comprising 5 quasimonomorphic mononucleotide repeats. This article compares the advantages of mono or dinucleotide repeats in determining microsatellite instability.     

Application of form features in digital cell analysis of non-Hodgkin''s lymphomas

The form of a biological cell nucleus can be characterized by the well-known circularity factor, which is derived from the area of an object and its circumference. More sophisticated form features are introduced, which are calculated from the curvature of an object (“bending energy”) or from invariant moments. To investigate the sensitivity of the various form features on controlled changes of form and the behaviour under rotation and scaling, algebraic curves similar to the form of real nucleus profiles are generated. Analysis of the shape characteristics of biological cells requires an extraction of the boundaries of the nuclei. This was performed by an edge detection algorithm using eight gradient masks followed by a contour tracing procedure with feedback. The suitability of the introduced form features for classification of different nucleus profiles on non-Hodgkin's lymphomas (NHL) was tested using a Bayes classifier.     

Comparative analysis of error-prone replication mononucleotide repeats across baculovirus genomes

Genome replication by the baculovirus DNA polymerase often generates errors in mononucleotide repeat (MNR) sequences due to replication slippage. This results in the inactivation of genes that affects different stages of the cell infection cycle. Here we mapped these MNRs in the 59 baculovirus genomes. We found that the MNR frequencies of baculovirus genomes are different and not correlated with the genome sizes. Although the average A/T content of baculoviruses is 58.67%, the A/T MNR frequency is significantly higher than that of the G/C MNRs. Furthermore, the A7/T7 MNRs are the most frequent of those we studied. Finally, MNR frequencies in different classes of baculovirus genes, such as immediate early genes, show differences between baculovirus genomes, suggesting that the distribution and frequency of different MNRs are unique to each baculovirus species or strain. Therefore, the results of this study can help select appropriate baculoviruses for the development of biological insecticides.     

Immunologic surface markers in non-Hodgkin''s lymphomas.

Tissues from 21 patients with non-Hodgkin's lymphomas were examined for immunologic cell surface markers. Patterns of distribution of complement receptor (CR) B lymphocytes and Fc receptor (FcR)-bearing histiocytes in tumor tissue were evaluated and compared to routine histologic preparations of the tumors and to normal tissue. The lymphomatous infiltrates from all 6 cases of nodular, poorly differentiated lymphocytic lymphoma (NPDLL) consisted of dense populations of CR B lymphocytes. Involved tissue from 7 of 8 patients with diffuse, poorly differentiated lymphocytic lymphoma (DPDLL) was predominately comprised of CR B lymphocytes. Discrete nodules of CR B cells were present in a lymph node replaced by DPDLL. FcR were identified on the cells from 1 of 3 cases of histiocytic lymphoma. None of the 4 cases of undifferentiated lymphoma possessed demonstrable surface markers in tissue section; however, the cell suspension from 1 case contained a high percentage of CR B cells. Both CR and T cell markers were present on the cells of DPDLL of childhood.     

Mutation frequency analysis of mononucleotide and dinucleotide repeats after oxidative stress

Many tumors exhibit genetic instability at the DNA sequence level in the form of frameshift mutations in simple repeats (microsatellite instability). A high level of microsatellite instability, such as that seen in hereditary nonpolyposis colorectal cancer (HNPCC), arises from defects in the mismatch repair pathway. A low level of microsatellite instability is found in some non-HNPCC-associated cancers, such as those of the breast and lung, and is not attributable to mismatch repair defects. We hypothesized that oxidative DNA damage may be at least partly responsible for the generation of microsatellite mutations in these tumors. We investigated whether oxidative DNA damage can induce microsatellite mutations in mismatch repair-proficient cultured cells. Telomerase-immortalized normal human fibroblasts were stably transfected with a plasmid containing a tk-neo fusion gene, such that the neo coding region was placed out of frame by the presence of an upstream microsatellite sequence. Cells were treated with H(2)O(2) and mutation frequencies were determined for G(17), A(17), and (CA)(17) repeats. Mutation frequencies of mononucleotide repeats in cells with the neo gene in the (+1) reading frame were reduced after treatment. No effect was observed in cells with the mononucleotide repeats in the (-1) reading frame. A small increase in mutation frequency was observed in cells with the (CA)(17) repeat. Our data suggest that diploid human cells may have protective mechanisms that prevent the induction of microsatellite mutations by a short exposure to high levels of oxidative stress.     

Expression of natural killer cell markers in non-Hodgkin''s lymphomas

One hundred forty-nine cases of non-Hodgkin's lymphoma were studied with a panel of monoclonal antibodies, including antibodies to natural killer (NK) cells--anti-NKH1, anti-Leu 7, and anti-Leu 11b. There were 95 B-cell, 51 T-cell, and three null cell lymphomas. Seventeen T-cell lymphomas (33 per cent) expressed NKH1, Leu 7, and/or Leu 11b. None of the B- or null cell lymphomas expressed the NK markers. In comparison with the NK-negative T-cell lymphomas, the NK-positive cases showed a predilection for the nasal and paranasal region. There was a more significant loss of the T-cell markers T3 (peripheral T cell) and T4 (T-helper cell) in NK-positive lymphomas. The difference was due to a high proportion of nasal/paranasal lymphomas, which were associated with a frequent loss of T-cell markers, among the NK-positive cases. However, a similar degree of loss of T-cell markers was observed among NK-positive and NK-negative nasal/paranasal lymphomas. We conclude that expression of NK markers occurs exclusively in a proportion of T-cell lymphomas, but not B-cell or null cell lymphomas. The reason this occurs predominantly in nasal and paranasal lymphomas is unknown.     

Pathological variables determining the prognosis of non-Hodgkin''s lymphomas

The aim of the study was to assess the role of pathological grade, cell proliferation, ploidy, immunophenotype and site in determining the prognosis of non-Hodgkin's lymphomas. Of particular interest was the relative value of grades derived from the Kiel classification as opposed to the National Cancer Institute (NCI) working formulation. The study consisted of 181 cases, treated in a relatively uniform way over an 18-month period spanning 1986. Using life table analysis, both NCI working formulation grade and Kiel grade correlated strongly with survival. However, the differences between grades were entirely due to an excess of early deaths in the high-grade and intermediate-grade categories. In patients surviving greater than 0.1 years (37 days), phenotype, site, ploidy and cell proliferation had no effect on survival. There was no evidence that intermediate-grade tumours, when subdivided into Kiel low- and high-grade types, differed in survival from tumours graded as low- or high-grade by both methods. However, NCI working, formulation high-grade tumours, especially those with a high proliferation rate, formed a group with a very high likelihood of death within 0.1 years.     

Identification of novel genes with somatic frameshift mutations within coding mononucleotide repeats in colorectal tumors with high microsatellite instability

We have systematically retrieved genes with coding mononucleotide repeats from sequence databases and analyzed them for mutations in tumors with high levels of microsatellite instability (MSI-H). We found somatic frameshift mutations in 7/13 genes previously not analyzed in MSI-H tumors. According to the frequency of mutations in MSI-H tumors, these genes could be divided into genes with high coding mononucleotide repeat instability (CMRI-H) and genes with low coding mononucleotide instability (CMRI-L). CMR-H genes were mutated in more than 9/38 and CMRI-L in less than 4/38 of MSI-H tumors. Four genes in our study were CMRI-H and could thus possibly play a role in the development of MSI-H tumors: TFE3 (9/38), TEF4 (12/38), RGS12 (11/38), and TCF1 (12/38). Our results suggest that systematic identification of genes with CMR in the sequence databases and determination of mutation frequency in MSI-H tumors might be a powerful tool for identification of new molecular targets in the development of MSI-H tumors.     

Prognostic importance of DNA flow cytometry in non-Hodgkin''s lymphomas.

Eighty one cases of non-Hodgkin's lymphoma were examined by DNA flow cytometry, using fixed embedded histological tissue. The frequency of detection of DNA aneuploidy and the values for S phase fractions depended on the histological subtype and grade of lymphoma. Twenty two of the patients with low grade centroblastic/centrocytic non-Hodgkin's lymphoma had repeat biopsies. Eleven of these patients remained histologically and cytometrically stable, but the remaining eleven transformed into high grade non-Hodgkin's lymphoma. The mean value for the S phase fraction in the initial biopsy specimens from patients which transformed was higher than that for patients whose lymphomas remained stable (p less than 0.001). It is proposed that estimates of S phase fraction prospectively identify patients with low grade non-Hodgkin's lymphoma at risk from transformation.     

Cell proliferation in non-Hodgkin''s lymphomas. Digital image analysis of Ki-67 antibody staining.

Ki-67 is a monoclonal antibody to a nuclear antigen present in cycling human cells but not in resting cells. The authors have performed immunoperoxidase on non-Hodgkin's lymphomas using Ki-67 antibody in order to correlate proliferation rates with tumor grade and type, and compare Ki-67 staining with S-phase content as determined by flow cytometry. Ki-67 staining of 109 sections was quantitated using a digital image analysis system (CAS 100). There was a significant difference among mean overall Ki-67 staining values in Working Formulation low (13.7%), intermediate (42.6%), and high grade tumors (57.9%, P less than 0.00001). The level of significance improved when a revised grading system was formulated based on proliferative activity, with the inclusion of diffuse large cell lymphomas in the high grade category. Within nodular and a few diffuse lymphomas, there were well-defined proliferation centers in which Ki-67 staining showed no correlation with grade. Flow cytometric DNA determination was performed on 74 specimens, and there was a positive correlation between Ki-67 positivity and S phase content (r = 0.66). It is concluded that Ki-67 staining of tissue sections is an alternative to flow cytometric quantitation of cell cycle activity in lymphomas, and provides the advantage of revealing histologic patterns of proliferation. By including G1 phase cells, Ki-67 staining allows a more complete determination of total cell cycle activity in lymphomas.