胃肠道间质细胞肿瘤43例临床及病理分析

目的:探讨胃肠道间质瘤临床表现和良性、潜在恶性、恶性的病理诊断标准,及其对临床评估预后的价值.方法:选用43例临床资料完整的病例,经免疫组化S-P方法测定CD117、CD34、SMA、S-100、NSE及组织化学Masson染色.结果:43例免疫组化阳性率CD117 40/43例(93.0%);CD34 34/43例(79.1%);CD117及CD34皆阳性30/43(69.8%),SMA 16/43例(37.2%)向平滑肌分化;S-100阳性或兼有NSE阳性14/43例(32.6%)向神经鞘分化;6/43例(14.0%)双向分化.良性5例,潜在恶性10例,恶性28例,预后与肿瘤病理判定密切相关.结论:胃肠道间质瘤的病理诊断除结合临床各项检查外,仍需依靠免疫组化测定(CD117及/或CD34),其中必须一项呈阳性者方能确定诊断.     

胃肠道间质瘤的诊断和治疗：附218例报告

目的 探讨胃肠道间质瘤(GIST)的临床病理特征及诊断治疗方法.方法 回顾性分析218例已行手术治疗的GIST患者的临床资料.通过光镜观察形态特征,应用免疫组织化学(SP法)检测CD117,CD34,S-100,波形蛋白(vimentin,VIM)和平滑肌肌动蛋白(SMA)的表达情况.结果 218例中,胃间质瘤152例(69.7%),小肠间质瘤27例(12.4%),结直肠间质瘤30例(13.8%),食管间质瘤9例(4.1%);其中恶性116例(53.2%).临床表现缺乏特异性,常以腹部肿物和消化道出血为首发症状.通过手术标本病理组织学和免疫组化检测均明确诊断.染色显示肿瘤组织中抗原表达:CD117呈弥漫强阳性,CD34和VIM多呈弥漫强阳性,SMA和S-100偶尔呈局灶或散在阳性,阳性率分别为100%,76.2%,38.1%,4.8%和4:8%,其阳性表达率与肿瘤良、恶性无关(P>0.05).58例随访6个月至3年,19例(均为恶性)发生复发和转移,因复发再次手术者5例.结论 CD117是诊断GIST的敏感而特异的标记物,但免疫表型与肿瘤良、恶性无关.手术整块切除是治愈GIST的惟一首选方法.     

胃肠间质瘤临床特征及CD117、CD34、DOG1联合检测的临床意义

目的分析胃肠间质瘤(GIST)临床特征及CD117、CD34、DOG1联合检测的临床意义。方法观察70例胃肠间质瘤患者临床特征及CD117、CD34及GOG1检查结果。结果 GIST好发于胃部(50.0%),以上腹胀痛、便血或腹部肿块等为主要表现。DOG1、CD117阳性率均明显高于CD34;CD117+DOG1+阳性率高于CD117+CD34+、CD34+DOG1+,差异均有统计学意义(P0.01)。不同GIST分级CD117、CD34、DOG1阳性表达比较,差异均无统计学意义(P0.05)。结论 CD117、DOG1对GIST敏感性均较高,联合检测能有效提高GIST诊断率,但不能判断GIST危险程度。     

52例胃肠道间质瘤的临床诊治及病理学分析

目的 探讨胃肠道间质瘤(GIST)的临床表现和诊治方法及病理、免疫组化特征.方法 对1995年1月至2007年12月武警湖北总队医院收治的52例胃肠道间质瘤患者进行回顾性分析,分析其临床治疗及病理学特征.结果 本组52例胃肠道间质瘤患者均接受手术治疗,其中45例为完全切除.52例患者中CD117阳性表达52例(100%),CD34阳性表达46例(88.5%). 结论 GIST以外科手术切除为主,完全切除很重要.GIST术前确诊率低,其确诊依赖免疫病理结果,CD117和CD34联合使用可协助诊断GIST.     

中高危胃肠道间质瘤患者组织中CD117、DOG-1、CD34、Ki67表达水平及临床意义

目的 探讨CD117、DOG-1、CD34、Ki67在中高危胃肠道间质瘤（gastrointestinal stromal tumors,GIST）中的表达水平、临床意义及其预后影响因素。方法 回顾性研究2015年1月至2018年1月至本院就诊的82例中高危胃肠道间质瘤患者,检测CD34、DOG-1、CD117、Ki67免疫组化标志物,分析患者一般情况、病理学特征、组织学表现、免疫组化结果以及1、3、5年总体生存期（overall survival,OS）和无复发生存期（recurrence-free survival,RFS）,研究患者5年OS、RFS的影响因素。结果 82例胃肠道间质瘤患者CD117、DOG-1、Ki67阳性分别为95.12%(78/82)、96.34%(79/82)、93.90%(77/82),明显高于D34阳性75.61%(62/82),差异有统计学意义（P<0.05）。1、3、5年OS分别为0%(0/82)、3.66%(3/82)、12.20%(10/82),1、3、5年RFS分别为2.44%(2/82)、28.05%(23/82)、76.83%(63/...     

胃肠间质瘤24例临床病理分析

为分析胃肠间质瘤（GISTs）的临床病理资料和免疫组化表达,对24例GISTs进行临床和病理资料分析及免疫组化检测。结果显示,24例GISTs发生部位包括小肠、结肠、直肠、肛门。其中梭形细胞为主型16例,上皮细胞为主型3例,混合细胞型5例。免疫组化Dog-1、CD117、CD34、Vimentin（＋）、SMA、S-100部分（＋）、Desmin（-）。结果表明,GISTs的病理诊断必须依据肿瘤大体形态、组织学、免疫组化结果综合判断;Dog-1、CD117及CD34在GISTs诊断中具有重要价值。     

42例胃间质瘤的临床及内镜分析

目的探讨胃间质瘤的临床及内镜特征。方法回顾性分析42例经病理证实的胃肠道间质瘤的临床和内镜资料,所有病例的组织均经免疫组织化学染色观察CD117、CD34、Vimentin、Actin和S-100的表达情况。结果本组42例胃间质瘤主要临床表现上消化道出血(占76%)。胃镜下表现:发生于胃底21例、胃体14例、胃窦7例;呈半球形隆起23例,息肉样隆起19例(45%),其中仅有3例内镜下活检证实为胃间质瘤。手术标本病理诊断为良性胃间质瘤17例、交界性14例,恶性11例。免疫组织化学检查CD117和CD34表达的阳性率分别为93%及79%,CD117、CD34在良性、交界性、恶性间质瘤中的表达均无显著性差异(P>0.05)。结论胃间质瘤临床表现无特异性,内镜下活检阳性率低,确诊多依靠手术病理及CD117、CD34的联合检测。     

胃肠道间质瘤组织TNC、CD55表达与临床病理特征及预后的关系

目的:探究胃肠道间质瘤组织中肌腱蛋白C(Tenascin-C,TNC)和CD55的表达及其与临床病理参数和预后之间的关系。方法:65例手术切除且经病理诊断为原发性胃肠道间质瘤组织样本,采用免疫组化的方法检测组织中TNC和CD55的表达,分析TNC和CD55表达与患者临床病理参数的关系;采用Kaplan-Meier生存曲线分析TNC、CD55的表达与患者预后的关系。结果:胃肠道间质瘤组织中TNC高表达率为27.7%(18/65),TNC的表达与肿瘤分化程度和TNM分期相关(均P<0.05);Kaplan-Meier生存曲线结果显示,胃肠道间质瘤组织TNC高表达的患者生存率较低。胃肠道间质瘤组织中CD55高表达率为24.6%(16/65),CD55的表达与胃肠道间质瘤肿瘤大小、远处转移以及TNM分期均相关(均P<0.05);Kaplan-Meier生存曲线结果显示,胃肠道间质瘤CD55低表达的患者术后生存率较高。结论:胃肠道间质瘤组织中TNC和CD55均存在表达,表达与胃肠道间质瘤患者的患者预后密切相关,TNC和CD55有可能成为胃肠道间质瘤预后评估的潜在标志物。     

胃肠道间质瘤的临床与病理关系分析

目的探讨胃肠道间质瘤的临床表现与病理学特征的关系。方法回顾分析本院1995～2003年收治的34例胃肠道间质瘤的临床和病理资料。结果本组病例中位年龄57岁,肿瘤位于胃20例(59%),小肠7例(20%),大肠4例(12%),食道3例(9%)。主要症状有腹痛(59%),消化道出血(26%)。病理诊断良性15例,恶性19例,良性肿瘤平均大小为4.1cm,恶性平均为10.8cm。CD34、CD117、S鄄100阳性表达率分别为65%、64%和47%,其阳性表达与肿瘤良恶性无关(P>0.05)。结论肿瘤免疫表型与良恶性无关。无论是良性还是恶性间质瘤,手术都是目前最重要的治疗手段。     

胃肠道间质瘤21例诊治分析

目的：探讨胃肠道间质瘤的临床表现、病理特征及诊疗措施。 方法：回顾性分析收治的21例胃肠道间质肿瘤的临床资料。 结果：13例（61.9%）患者首发症状为消化道出血,5例（23.8%）为腹部胀痛不适;12例（57.1%）胃肠道间质瘤发生在胃。瘤细胞为梭形或上皮样,或两者混合存在。21例中20例CD117（＋）,9例CD34（＋）。全组患者均行手术治疗,围手术期无患者死亡。术后1年存活率为90.1％,3年存活率为76.2％,5年存活率为61.9％。 结论：胃肠道间质瘤无特异的临床表现,术前明确诊断较困难。因瘤细胞有较独特的免疫组化表型,确诊依靠病理学及免疫组化,其中CD117阳性率大于95%。治疗主要依靠手术联合分子靶向药物的综合治疗。     

Lymphocyte subtypes CD3+, CD19+, CD16+CD56+, CD4+, CD8+, and CD3+HLA-DR+ in peripheral blood obtained from patients after thoracic organ transplantation

Introduction

The aim of this study was to assess peripheral blood lymphocyte subtypes (CD3⁺, CD19⁺, CD16⁺CD56⁺, CD4⁺, CD8⁺, and CD3⁺HLA-DR⁺) obtained from thoracic organ recipients at various periods after transplantation.

Material and Methods

Seventeen patients after lung transplantation (LT) and 5 patients after heart transplantation (HT) included 13 males (76.5%) and 4 females (23.5%) of overall mean age at the time of transplantation of 46.7 ± 11.55 years and mean body mass index of 21.1 ± 4. Lymphocyte phenotypes were estimated using Simultest IMK Plus.

Results

A significant decrease in lymphocytes of the majority of subtypes was observed at 1 year posttransplantation compared with normal ranges: CD19⁺ B lymphocytes in 56% of patients, CD8⁺ T cells among 48% and CD16⁺CD56⁺ natural killer elements, 56%. In contrast, there were increased numbers of activated lymphocytes (CD3⁺HLA-DR⁺). Beyond the 1-year observation, we observed a trend to normalize parameters among the majority of subjects.

Conclusion

A clear tendency to a decrease number of peripheral blood lymphocytes of various subtypes was observed among thoracic organ recipients in the first year posttransplantation with the exception of activated HLA-DR⁺ cells. After the first year, there was slow restoration of lymphocytes.     

Upregulation of CD40, CD80, CD83 or CD86 on alveolar macrophages after lung transplantation.

BACKGROUND: Alveolar macrophages (AMs) are known to be poor antigen-presenting cells, and lack the accessory molecules such as CD40, CD80 or CD86 to activate T cells. The question raised is about the potential changes in phenotypes after lung transplantation, particularly during acute rejection episodes. METHODS: The present study analyzed the phenotype of AMs longitudinally in 45 lung transplant patients, between August 1997 and April 2002, with a follow-up period of 27.2 +/- 2.5 (mean +/- SEM) months. There were 7.7 +/- 0.6 bronchoalveolar lavage (BAL) assessments performed per patient (i.e., 345 BALs), simultaneously with transbronchial biopsies. Transplantation was soon followed by a progressive upregulation of CD40 on 49.7 +/- 8% of AMs during the first month, and this marker remained elevated at 60 +/- 8% after 5 years. RESULTS: Both CD86 and CD80, as well as CD83, a marker of dendritic cells, were enhanced for most AMs during Grade A2 and A3 rejection episodes. A correlation was found between expression of CD83 and CD86, but not between CD1a and CD86. Immunohistology confirmed that CD40-positive cells in the alveoli corresponded to AMs and to some dendritic cells in the basal layers of the airways. In vitro studies showed that harvested AMs with these enhanced accessory molecules remained poor stimulators of allogeneic cells, a phenomenon that may be related to the ongoing immunosuppressive treatments. CONCLUSIONS: AM phenotypes showed marked changes during early or late acute rejection episodes, acquiring CD80, CD83 and CD86, while CD40 expression was further enhanced. This finding may provide clues on how to monitor the tolerance of transplanted lungs and may also provide new insights into the pathophysiology of lung transplantation.     

CD27/CD70, CD134/CD134 ligand, and CD30/CD153 pathways are independently essential for generation of regulatory cells after intratracheal delivery of alloantigen

BACKGROUND: We investigated whether blockade of tumor necrosis factor receptor-ligand pathways could generate regulatory cells induced by intratracheal delivery of alloantigen. METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of splenocytes (1x10(7)) from C57BL/10 (H-2b) mice and intraperitoneal administration of monoclonal antibody (mAb) specific for CD70, CD134 ligand (CD134L), CD153, or CD137L. Seven days later, C57BL/10 hearts were transplanted into pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of splenocytes (5x10(7)) from pretreated CBA mice and transplantation of a C57BL/10 heart on the same day. RESULTS: Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST] 12 days). Pretreatment with intratracheal delivery of C57BL/10 donor splenocytes prolonged graft survival significantly (MST 84 days). Mice given intratracheal delivery of alloantigen plus anti-CD70, anti-CD134L, or anti-CD153 mAb, but not those given intratracheal delivery of alloantigen plus anti-CD137L mAb, rejected their graft acutely (MST 16, 14, 10, and 65 days, respectively). Adoptive transfer of splenocytes from mice pretreated with intratracheal delivery of alloantigen plus anti-CD70, CD134L, or CD153 mAb did not prolong survival of C57BL/10 cardiac grafts in naive secondary CBA recipients (MST 14, 11, and 11 days, respectively), whereas adoptive transfer of splenocytes from mice given intratracheal delivery of alloantigen plus anti-CD137L mAb did (MST 75 days). CONCLUSION: The CD27/CD70, CD134/CD134L, and CD30/CD153 pathways are independently required for generation of regulatory cells in our model.     

Cross-species costimulation: relative contributions of CD80, CD86, and CD40

BACKGROUND: The response of human CD4+ T cells against porcine cells is of comparable magnitude to that induced by human leukocyte antigen-mismatched allogeneic cells. This reflects productive interactions between key costimulatory molecules across the species barrier. Inhibition of these molecular interactions will be crucial in overcoming CD4+ T-cell-mediated rejection of xenografts. We have performed a detailed investigation to determine the expression profiles and relative contributions of the three key costimulatory molecules in the porcine-human xenogeneic response. Whereas only porcine CD86 is constitutively expressed on resting endothelial cells, both CD40 and CD80 are rapidly expressed after activation. All three costimulatory molecules are expressed by professional antigen-presenting cells. METHODS: We have isolated full-length cDNA clones for human and porcine CD80, CD86, and CD40. Human fibroblast cell lines (M1) coexpressing DR1 were transfected with these cDNAs and used in mixed lymphocyte reactions and flow cytometric studies in vitro. RESULTS: These data provide the first characterization of the expression profile and functional role of porcine CD80. Functional assays demonstrate that pCD40, pCD80, and pCD86 are independently capable of costimulating human CD4+ T cells, albeit with differing kinetics. Proliferative responses were of comparable magnitude to those obtained when costimulation was provided by human CD40, CD80, and CD86. CONCLUSIONS: These data have implications for therapy targeting the direct pathway of xenorecognition; costimulatory molecule blockade must be directed against both the B7/CD28 and CD40/CD40L pathways.     

Peripheral T-cell lymphomas expressing CD30 and CD15

Coexpression of CD30 and CD15 is typically associated with classic Hodgkin's lymphoma (HL). Peripheral T-cell lymphomas (PTCLs) can often display histologic features that simulate classic HL. However, reports of PTCLs coexpressing both CD30 and CD15 have been infrequently described. We report 11 cases of PTCL in which at least a subset of the neoplastic cells coexpressed CD30 and CD15. The patients included 4 women and 7 men and age ranged from 43 to 83 years (median, 62 years). Nine of 10 patients had advanced stage III or IV disease at presentation. Nodal involvement predominated in 8 of 11 patients, whereas 2 patients presented primarily with skin involvement. Two distinct groups were identified based on morphologic and immunophenotypic features. The first group of 5 cases had histologic features mimicking classic HL with CD30+, CD15+ Reed-Sternberg (RS)-like cells in an inflammatory background of varied extent and composition. The background lymphoid cells showed minimal cytologic atypia. The RS-like cells were negative for CD20 and CD79a in all cases, and CD45 expression was absent in 4 of 5 cases. The RS-like cells expressed CD25 and at least one T-cell-associated marker in all cases. The background T-cell population showed convincing subset predominance in 4 of 5 cases and loss of T-cell-associated antigens in 3 of 5 cases and coexpression of CD30 and CD15 in one case. The second group of 6 cases had morphologic features more in keeping with PTCL than classic HL. The proportion of neoplastic cells coexpressing CD30 and CD15 varied. Loss of T-cell antigens was noted in all cases and CD4 predominated in 4 of 5 cases. Three of the 6 cases expressed CD45. PCR analysis revealed clonal T-cell receptor gamma (TCR-gamma) chain gene rearrangements in 9 of 11 cases, but no immunoglobulin heavy (IgH) chain gene rearrangements. In situ hybridization studies for Epstein-Barr virus were negative in all cases. In some PTCL cases, the overlap with classic HL can be striking, and combined immunophenotypic and molecular studies are often necessary to confirm the diagnosis.     

CD4+CD25+ cells regulate CD8 cell anergy in neonatal tolerant mice

BACKGROUND: Injection of neonatal BALB/c mice with semi-allogeneic splenocytes leads to antigen-specific tolerance lasting into adulthood. Tolerant mice accept A/J skin grafts and fail to generate CD8 cytotoxic T lymphocyte (CTL) activity against A/J targets. Anergic CD8 T cells are present in tolerant mice, and CD4 regulatory cells function to maintain CD8 cell anergy. METHODS: Neonatal BALB/c mice were injected with 108 live CAF, splenocytes, and mice were deemed tolerant by accepting A/J grafts over 40 days. CD8 cell proliferation was measured by in vitro incorporation of bromodeoxyuridine coupled with fluorescence-activated cell sorter analysis. Alloantigen-specific cytotoxicity was tested using 51Cr release assays of A/J or third-party targets. RESULTS: We demonstrate that A/J-specific anergic CD8 cells are present in neonatal primed mice that develop tolerance but not in neonatal primed mice that reject A/J skin grafts. Anergic CD8 cells show decreased proliferation and no CTL activity against A/J targets. Addition of interleukin-2 (IL-2) to unfractionated cultures fails to restore CTL activity against A/J targets. However, addition of IL-2 to CD4-depleted cultures restores A/J-specific CD8 CTL activity. Removal of CD4+/CD25+ cells, but not CD4+/CD25- cells, also restores CD8 CTL activity against A/J in the presence, but not the absence, of IL-2. Moreover, when added back into cultures, purified CD4+/CD25+ cells from tolerant mice inhibit the generation of CD8 CTL against A/J targets. CONCLUSION: These data indicate that CD8 anergy is associated with the state of tolerance, and that CD4+CD25+ cells from tolerant mice function to maintain A/J-specific CD8 cell anergy in vitro.     

CD52 ligation induces CD4 and CD8 down modulation in vivo and in vitro

To successfully induce donor-specific tolerance after immune depletion, it is essential to understand the residual and recovering immune system in the context of the depleting agent because the properties of such a recovering immune system differ based on the depleting agent used. In this study, we investigate the phenotypic and functional characteristics of T cells exposed to Campath-1H in vivo and in vitro. Recovering T cells demonstrated down modulated surface CD4 and CD8 (by flow cytometry) for up to 45 days after Campath-1H administration. Additionally, these T cells had an activated phenotype. To determine whether this CD4/8 down modulation was due to T-cell activation only or in part due to Campath-1H, whole blood from healthy volunteers was exposed to Campath-1H and the surviving lymphocytes isolated. Flow cytometry revealed a dose-dependent down modulation of CD4/8 without T-cell activation. Additionally, these Campath-1H-treated T cells were immunocompetent as indicated by increased surface CD69 and interleukin-2 (IL-2) production following stimulation by soluble anti-CD3 mAb. In conclusion, Campath-1H by itself down modulates surface CD4 and CD8 without activating T cells.