蕈样肉芽肿凝集素免疫病理研究

作者用生物素-抗生物素-过氧化物酶复台物(ABC)法对17例蕈样肉芽肿(MF)的12种凝集素受体进行了免疫组化观察。10例扁平苔藓（LP）作为对照组。PNA、DBA、SBA、BSA、PSA、SJA和UEA-1七种凝集素受体在MF及LP均未见表达，RCA-1、WGA、Con—A、LcA及PHA在MF及LP则有表达。结果提示：MF和LP中淋巴细胞凝集素受体表达有所不同；但在分化程度上都处于成熟阶段。     

花生凝集素受体在子宫内膜癌中的定位研究

应用生物素交联的花生凝集素(PNA)对子宫内膜腺癌85例、正常子宫内膜8例、单纯型增生内膜7例、腺瘤型增生8例、不典型增生13例进行免疫组织化学研究。结果,PNA受体的阳性率在正常内膜、不同类型增生内膜及腺癌中逐渐增高,PNA受体的定位分布则从腺体的腔缘移向胞浆,RNA受体在子宫内膜腺癌中的过量表达和胞浆内的定位改变可能和内膜腺癌的发生及分化有关。     

5种凝集素受体在胃癌及慢性胃炎粘膜组织中的表达

应用streptavidin-gold探针及免疫金—银染色法,观察PHA、DBA、UEA、WGA、ConA5种凝集素受体在胃癌及慢性胃炎粘膜组织中的表达。结果显示,胃癌与慢性胃炎之间,以及不同组织类型胃癌之间的凝集素受体表达存在一定差异,比较这些差异可能有助于胃癌的诊断和组织分型。结果还显示,萎缩性胃炎粘膜组织的PHA受体表达与胃癌相似,提示二者在糖代谢紊乱方面可能有共同之处。     

Brenner瘤细胞分化的凝集素受体标记

研究７种生物素化的凝集素对卵巢Ｂｒｅｎｎｅｒ瘤不同分化方向和分化性质瘤细胞的标记特点，麦胚素、花生素受体在瘤细胞呈顶浆型表达是瘤细胞向腺上皮分化的标志；双花扁豆素受体瘤细胞膜阳性显示其向鳞状上皮分化倾向；ＷＧＡ、ＰＮＡ、兀鹰素（ＢＳ－１）和刀豆素在瘤细胞浆内弥漫性结合增强表明Ｂｒｅｎｎｅｒ瘤由良性、增生性向恶性转化。凝集素受体表达差异可做为Ｂｒｅｎｎｅｒ瘤细胞的分化标志，体现该瘤上皮成分分化，失分     

恶性淋巴瘤凝集素受体的研究

对32例恶性淋巴瘤(ML)的凝集素受体研究结果表明:ML组织中含有多种特异性糖蛋白,可被多种凝集素标记。刀豆凝集素(ConA),麦胚凝集素(WGA),豌豆凝集素(PSA),蓖麻凝集素(RCA)有较强的敏感性,可作为稳定可靠的标志。凝集素受体不仅有胞浆型、胞膜型定位,尚有核膜型定位。ConA受体在肿瘤组与非肿瘤对照组的核膜型定位上表现出很大的不同(P值<0.01),这具有实际应用意义。PSA的显色反应提示了该种凝集素受体的分布可能与淋巴瘤分化程度有关。RCA对R—S细胞的标记结果,不支持R—S细胞来源于组织细胞的学说。     

乳腺癌凝集素受体与雌激素受体关系及意义的探讨

本文运用亲合组化和荧光组化法对35例乳腺癌的8种凝集素受体和雌激素受体进行了对比研究,结果发现仅花生凝集素受体(PNA—R)与雌激素受体(ER)呈正相关(P<0.005)这种相关关系提示。可以通过PNA亲合组化对石蜡切片档案材料进行回顾性研究,以推测乳癌患者的ER状况,为乳腺癌的内分泌治疗提供依据     

胆囊病变组织凝集素受体和癌胚抗原定位检测

应用ABC免疫组化技术对49例胆囊病变组织进行凝集素受体和癌胚抗原(CEA)的定位检测。结果表明胆囊癌的西非单叶豆(BSL)、双花藊豆(DBA)和扁豆(LCA)受体丢失,花生(PNA)受体和CEA表达明显增加,而且PNA受体与CEA表达呈正相关。     

亲和组织化学在软组织肿瘤病理诊断中的应用

亲和组织化学(Affinity Histochemistry)是利用一种物质对某一种组织成份的高度亲和能力发展起来的细胞、组织化学。亲和组织化学包括抗原与抗体、凝集素与糖类、生物素与抗生物素、葡萄球菌A蛋白与HgG、阳离子与阴离子、激素与受体、维生素、糖、以及类脂质等。亲和组织化学是免疫组织化学的进一步扩大和发展,比单纯的免疫组化方法     

简报

软组织肿瘤的凝集素免疫组织化学研究软组织肿瘤的凝集素免疫组织化学研究,国外只限于少数几种凝集素对个别软组织肿瘤,国内尚未见报道。解放军第九八医院病理科茅建忠等报道,他们采用12种生物素化凝集素作为探针,检测了软组织肿瘤凝集素受体的分布特点,以判断肿瘤性质和组织起源,探讨其在软组织肿瘤诊断中的价值。     

软组织肿瘤的凝集素组织化学

应用ABC免疫组化技术对134例软组织肿瘤进行12种凝集素受体的定位检测,了解其受体的分布特点,以判断肿瘤性质和组织起源,探讨其在软组织肿瘤诊断中的价值。结果发现不同组织源性及良、恶性软组织肿瘤凝集素受体表达不一.因此作者认为有些凝集素可作为软组织肿瘤诊断或鉴别诊断、良恶性区分的标志,(?)组织肿瘤的定性、定源提供了新的参数.     

Magnetic fields (MF) of 50 Hz at 1.2 microT as well as 100 microT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells.

Magnetic fields (MF) of 60 Hz at 1.2 microT were previously shown to inhibit the antiproliferative effect of melatonin on MCF-7 cells (Liburdy,R.P., 1993, J. Pimeal Res. 14, 89-97). In addition, three laboratories (Blackman,C.F. and Benane,S.G., 1998; Luben,R.A. and Morgan,A.P., 1998; Morris,J.E., Chrisler,W.B., Miller,D.L., Sasser,L.B. and Anderson,L.E., 1998; 20th Annual Meeting of the Bioelectromagnetics Society, At. Pete Beach, FL) independently reported results consistent with this finding. In this study, we investigated the molecular basis of the biological effects of MF using MCF-7 cells. Only 1a melatonin receptors were identified by the [125I]melatonin binding assay and RT-PCR analysis. Moreover, preceding exposures to MF of 100 microT for 3, 5 and 7 days blocked the melatonin-induced inhibition of cAMP accumulation in a time-dependent manner, while none of the melatonin receptor functions or GTPase and adenylyl cyclase activities were affected. Estrogen-evoked cell proliferation was not altered by MF either. Exposure to 1.2 microT MF exerted the same effects on the melatonin-signaling pathway as that to 100 microT. Thus, this is the first study to provide evidence that MF may cause uncoupling of signal transduction from melatonin receptors to adenylyl cyclase.     

CD30+ Neoplasms of the Skin

Cutaneous T-cell lymphomas (CTCLs) are subdivided by lesion morphology, behavior, and surface receptors. Mycosis fungoides (MF) and Sézary syndrome (SS) are derived from CD4+ effector or central memory T-cells respectively. MF presents clinically as patches, plaques, or tumors, and SS presents with erythroderma. After MF/SS, the next most common CTCLs are CD30+ lymphoproliferative disorders: self-regressing lymphomatoid papulosis (LyP) or tumors of anaplastic large-cell lymphoma (ALCL), which express high levels of tumor necrosis factor death receptor member 8, also called CD30. Although MF is not considered to be a CD30+ lymphoproliferative disorder, MF may co-exist with LyP lesions, and MF may express CD30, especially in the setting of large-cell transformation. The development of targeted therapy for CD30+ CTCLs will help in understanding the importance of the CD30 death receptor in pathogenesis and will improve treatment options.     

CD8+ T cells in cutaneous T-cell lymphoma: expression of cytotoxic proteins, Fas Ligand, and killing inhibitory receptors and their relationship with clinical behavior.

PURPOSE: We investigated the number, phenotype, and prognostic significance of CD8+ T cells in patients with mycosis fungoides (MF) and CD30- primary cutaneous large T-cell lymphoma (PCLTCL). PATIENTS AND METHODS: Immunohistochemical stainings for CD8, granzyme B (GrB), T cell-restricted intracellular antigen (TIA-1), Fas ligand (FasL), and killer-cell inhibitory receptors (KIRs; CD95, CD158a, and CD158b) were performed on 83 first-diagnostic biopsy samples obtained from patients with plaque-stage MF (n = 42), tumor-stage MF (n = 20), and CD30- PCLTCL (n = 21). RESULTS: Serial sections and double-staining experiments showed that the large majority of CD8+ T cells in MF and CD30- PCLTCL expressed TIA-1 and FasL, whereas only a minority expressed GrB, which suggested that these CD8+ T cells were partly activated cytotoxic T lymphocytes (CTLs). These CD8+ CTLs never or rarely expressed KIRs. This phenotype was a constant feature of CD8+ CTLs and did not alter with disease progression. In contrast, the median percentage of CD8+ CTLs in plaque-stage MF (22%), tumor-stage MF (7%), and CD30- PCLTCL (3%) differed significantly (P < .0001) and was associated with a significant decrease in 5-year survival. Also within the group of tumor-stage MF, a significant relation between CD8+ CTLs and survival was found. Multivariate analysis in the total group of MF demonstrated that both skin stage and percentage of CD8+ CTLs were independent parameters of survival. CONCLUSION: Our results demonstrated that partly activated CD8+ CTLs were present in CTCL and that high proportions of these cells correlated with a better prognosis. This suggested that these CD8+ CTLs could play an important role in the antitumor response in these conditions.     

Elevated thrombopoietin levels in patients with myelofibrosis may not be due to enhanced production of thrombopoietin by bone marrow

Thrombopoietin (TPO) is recognized as the primary regulator of megakaryocyte and platelet production. Two alternative hypotheses for the mechanism of regulation have been proposed: (1) platelet and/or megakaryocyte mass regulate circulating TPO levels by binding to TPO through TPO receptors (c-MPL), with subsequent internalization and degradation of the protein; (2) TPO mRNA produced by bone marrow (BM) stromal cells or BM cells modulates blood TPO levels or platelet counts. In myeloproliferative disorders (MPD), including primary myelofibrosis (MF) and essential thrombocythemia (ET), elevated blood TPO levels occur despite increased platelet and megakaryocyte mass. Therefore, in these diseases, elevated blood TPO levels cannot be explained by the first mechanism. The present study, was designed to measure TPO mRNA production by BM mononuclear cells and BM stromal cells using a relative RT-PCR technique, to verify the second mechanism. We found no increase of TPO mRNA production in either BM cells or in BM stromal cells in patients with MF and ET. Furthermore, in those patients with MF who had elevated plasma TPO levels, TPO mRNA levels in bone marrow fibroblasts (BMFs) or BM cells were not elevated as compared with controls. Therefore, we concluded that in patients with MF, the elevated plasma TPO levels are not due to enhanced production of TPO mRNA either by BMF, or BM cells. The TPO receptor (c-MPL) abnormalities including reduced MPL protein levels or defective TPO induced signal transduction pathways are the likely mechanisms.     

Biological characteristics and estrogen and progesterone receptors in mammary carcinoma induced in male Sprague-Dawley rats by a series of intragastric intubations of 7,12-dimethylbenz(a)anthracene

Biological characteristics and estrogen (ER) and progesterone (PR) receptors were studied in male mammary carcinomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) in male inbred Sprague-Dawley rats (MM). DMBA-induced carcinomas in females (MF) were used as controls. In 36 of 44 female rats given 20 mg DMBA once by gastric intubation at 50 days of age, MF with microscopic characteristics of cystic papillary adenocarcinoma developed 124 +/- 49 (S.D.) days after challenge. In all of the 42 male rats given 10 mg DMBA at 14-day intervals for 14 weeks starting from 28 days of age. MM with microscopic characteristics of medullary adenocarcinoma developed 106 +/- 21 days after the first intubation of DMBA. The growth of primary MM was unaffected by orchiectomy or estrogen. Eighty to 100% of the MM transplanted in the four groups could grow in intact female rats, ovariectomized female rats, intact male rats, and castrated male rats, while the transplanted MF could grow only in intact female rats. The histology of MM was unchanged in primary and transplanted tumors under various hormonal conditions. ER were present in almost all of the hormone-independent primary and transplanted MM, although the levels for cytosol ER in MM were significantly lower than those in MF. Injection of 10 micrograms 17 beta-estradiol induced marked synthesis of PR in primary and transplanted MM, even 24 and 48 hr after the 17 beta-estradiol injection. These findings show that MM are hormone independent but, like hormone-dependent female tumors, contain ER and estrogen-dependent PR.     

Gene transfer of pro-IL-18 and IL-1beta converting enzyme cDNA induces potent antitumor effects in L1210 cells.

We report in a murine model of acute lymphoid leukemia L1210 the potent antitumor efficiency of a combinatorial delivery of pro-IL-18 gene modified L1210 (Lp18) and IL-1beta converting enzyme (ICE) gene modified L1210 (LpICE). Live leukemia cells Lp18 or Lp18 plus LpICE showed apparently reduced leukemogenicity with a survival rate of 40 or 50% at 50 days after intraperitoneal (i.p.) inoculation of a lethal dose of cells, respectively. Combination of Lp18 and LpICE was capable of inhibiting accumulation of bloody ascites, synergistically superior to Lp18 or LpICE alone. All surviving mice were rechallenged with parental L1210 cells at day 50, and all survived up to day 80, suggesting that gene-modified cells induced immune protection. Moreover, NK cytotoxicity and CTL activity were both enhanced in mice injected with Lp18, especially Lp18 plus LpICE. Levels of IFN-gamma were not altered significantly by inoculation of Lp18 or Lp18 plus LpICE. Our results demonstrate that IL-18 is a useful candidate gene in gene therapy of lymphoma or lymphoid leukemia, and ex vivo combinatorial delivery of Lp18 plus LpICE either as a single approach or as an adjunct to concomitant radiotherapy or chemotherapy, may be more efficient in a situation of minimal residual disease.     

Disease and Clinical Characteristics of Patients With a Clinical Diagnosis of Myelofibrosis Enrolled in the MOST Study

BackgroundClinical characteristics and treatment patterns of patients with lower-risk myelofibrosis (MF) are not well described. This analysis from the MOST (NCT02953704) assessed the demographic and clinical characteristics and treatment patterns of patients with the clinical diagnosis of lower-risk MF at enrollment.Patients and MethodsMOST is an ongoing, prospective, observational study in patients with clinical diagnoses of MF or essential thrombocythemia enrolled at clinical practices throughout the United States. Patients included in the MF cohort (≥18 years of age) had low-risk MF by the Dynamic International Prognostic Scoring System or intermediate-1 (INT-1) risk MF (by age >65 years only) at enrollment. Patient data were entered into an electronic case report form during usual-care visits over a planned 36 month observation period.ResultsTwo hundred five patients were eligible for this analysis (low risk, n = 85; INT-1 risk, n = 120; median age, 68 years [range, 35–88]); 166 patients (81.0%) had mutation testing results available. The median time from MF diagnosis to enrollment was 1.8 years. Hemoglobin and hematocrit levels were below the normal range in 50.5% and 48.7% of patients, respectively. Nearly all (98.0%) patients had comorbid conditions, most commonly hypertension (49.8%). Fatigue was the most common physician-reported MF symptom (30.7%). At enrollment, 55.6% of patients were receiving MF-directed monotherapy, most frequently hydroxyurea (46.5%) or ruxolitinib (40.4%).ConclusionFuture longitudinal analyses of data from MOST will help identify unmet needs and characterize how patients with lower-risk MF are managed throughout the disease course.     

Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases

According to current World Health Organization (WHO) criteria, counting mitotic figures (MF), which is equal to the mitotic index (MI), on paraffin sections stained with hematoxylin and eosin (HE) is one of the recognized classification methods for meningiomas. However, it is not always easy to find the area of highest mitotic activity, and there are different perspectives among pathologists with regard to differentiating MF from non-MF, i.e., which are apoptotic figures and which are crushed or distorted cells. Moreover, there is an issue of overgrading in meningiomas with preoperative feeder embolization. Recently, anti-phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker for meningioma grading. In this study, we attempted PHH3 immunostaining for our meningioma cases and verified not only the sensitivity of PHH3 immunostaining but also that of its usefulness in grading meningiomas. Forty-five initial histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic) were reviewed according to current WHO criteria based on counting MF on HE-stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1 labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily identified and permitted rapid recognition of the areas of highest mitotic activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no significant differences of PHH3-MI between cases with and without feeder embolization were demonstrated. As such, PHH3 may be a sensitive and useful marker for meningioma grading as based on the MF.     

Immune function abnormalities in peripheral blood mononuclear cell cytokine expression differentiates stages of cutaneous T-cell lymphoma/mycosis fungoides.

PURPOSE: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) characterized by neoplastic skin-homing T cells. To better understand the immunopathogenesis of MF, we analyzed the functional ability of peripheral blood mononuclear cells (PBMC) from early and late MF/CTCL patients to express cytokine genes. In late stage MF/CTCL, patients were separated into those with blood involvement (+B) and without blood involvement (-B). EXPERIMENTAL DESIGN: We analyzed T(H)1 (interleukin 2 (IL-2), IFN-gamma), T(H)2 (IL-4, IL-5, IL-10, IL-13), and T(H)17 (IL-17) cytokine gene expression from activated PBMCs from normal (n = 12), psoriasis (n = 6), early MF/CTCL (n = 11), and late MF/CTCL+B (n = 4) and MF/CTCL-B (n = 3) by quantitative real-time PCR. RESULTS: PBMCs from early MF/CTCL and psoriasis showed higher induction of IL-2, IL-4, and IFN-gamma genes than those from normal and late MF/CTCL-B and MF/CTCL+B (P < 0.05) in descending order. PBMCs from late MF/CTCL-B exhibited generally the highest level of IL-5, IL-10, IL-13, and IL-17 expression compared with the other groups. PBMCs from early MF/CTCL and late MF/CTCL-B had similarly elevated IL-13 and IL-17. Of all groups, PBMCs from late MF/CTCL+B had the lowest levels of IL-2 (P < 0.05), IL-4, IFN-gamma, IL-13, and IL-17. CONCLUSIONS: The different pattern of cytokine gene expression suggests a change in immune function in MF/CTCL from early MF/CTCL to late MF/CTCL-B to late MF/CTCL+B. These stages are consistent with localized disease associated with an anti-tumor immune response and late MF/CTCL associated with a loss of immune function mediated by malignant T cells that share regulatory T cell-like properties.     

Dermal dendrocytes and T-cells in canine mycosis fungoides. Support for an animal model of human cutaneous T-cell lymphoma.

BACKGROUND. An extensive upper dermal network of human Thy-1+/Factor XIIa+ dermal dendrocytes (DD) exists in human mycosis fungoides (MF). METHODS. Immunophenotyping and morphologic studies on serial frozen and paraffin sections from 15 cases of canine MF were performed to see if a similar network exists in this disease, as has been proposed as an animal model of human MF. Primary antibodies were anti-human Factor XIIIa, Factor XIIIs, anti-canine Thy-1, CD4, CD8, CD18, CD45RA, Class II, MAC387, KP-1, EBM-11, and several other pan-T, pan-B, and pan monocyte markers. RESULTS. Thy-1+/Factor XIIIa+DD were seen in all cases and confirmed on identical cells by double immunofluorescence. These were seen throughout the upper dermis, similar to DD in human MF. Canine DD expressed the macrophage marker 2A2+, and were Class II+, CD4+, CD8-, CD18+, EBM11-, Factor XIII-, MAC387-, and KP-1. Epidermal and dermal lymphocytes in canine MF were Thy-1-, CD4+, CD8-, CD18+, CD45RA-, EBM11-, MAC387-, Factor XIIIa-, Factor XIIIs- in some cases, whereas others had a predominance of CD8+ lymphocytes. CONCLUSIONS. Thus, canine MF is immunophenotypically similar to human MF. Additional support for this disease as a model of human MF is demonstrated by the rich network of Thy-1+/Factor XIIIa+ DD in the upper dermis of canine MF similar to human MF.