恶性上皮性肿瘤中CK20的表达及其临床意义

目的　研究单克隆抗体CK2 0在恶性上皮性肿瘤和卵巢转移性腺癌组织中的表达及其意义。方法　应用S P法对鼻咽非角化性癌、乳腺浸润性导管癌、肺的鳞癌和腺癌、卵巢黏液性囊腺癌、胃腺癌和结肠直肠腺癌各组总计 6 7例和 4 1例分别进行了CK2 0和CK19检测。结果　CK2 0阳性率 :肺腺癌 1/ 7(14 3% ) ,卵巢浆液性和黏液性腺癌 3/ 12 (33 3% ) ,胃腺癌 3/ 9(33 3% ) ,结肠直肠腺癌组 2 1/ 2 2 (95 5 % ) ,其他癌组织均呈阴性。结肠直肠腺癌组组与其他各组间比较差异有显著性 (P <0 0 1)。CK19在上述 4 1例癌组织中均呈强阳性表达。结论　CK2 0表达对鉴别结肠腺癌和直肠腺癌与肺腺癌和乳腺浸润性导管癌具有高度特异性和较高的敏感性 ;CK2 0高表达对鉴别卵巢原发性腺癌与卵巢的结肠腺癌或直肠腺癌转移具有一定的意义     

乳腺上皮-肌上皮性肿瘤4例临床病理学分析

目的：探讨乳腺上皮-肌上皮性肿瘤(epithelial-myoepithelial tumor of breast)的临床病理学特点、免疫表型、诊断及鉴别诊断。方法：对4例乳腺上皮-肌上皮性肿瘤的临床特点、组织形态学及免疫组织化学结果进行分析,并复习相关文献。结果：患者：男性1例,女性3例,平均年龄51岁(27~63岁)。4例肿瘤直径1.5~3.0 cm(平均2.0 cm),无包膜,切面灰白色。显微镜下可见肿瘤由双相增生的肌上皮细胞和腺上皮细胞构成,肌上皮细胞环绕腺上皮细胞构成特征的套管结构。免疫组织化学染色,腺上皮细胞表达CK8/18、CK7,肌上皮细胞表达p63、Calponin、CK5/6。1例诊断为腺肌上皮瘤(adenomyoepithelioma,AME),3例诊断为伴有癌的腺肌上皮瘤(恶性腺肌上皮瘤, malignant adenomyoepithelioma,MAME)。结论：乳腺上皮–肌上皮性肿瘤是少见的肿瘤类型,需与导管内乳头状瘤、化生性癌等鉴别。     

波形蛋白与肿瘤病理诊断的研究

Vimentin was isolated and purified from the pig eye lens by homogenization, ultracentrifugation, extraction in urea buffer and preparative electrophoresis. It was identified with SDS-PAGE and rabbit anti-vimentin was raised against the purified vimentin. The specificity of anti-vimentin was examined with immunohistochemical technique and double immune diffusion. Results showed that the vimentin antibody possessed good specificity for mesenchyme-derived cells. Tumor tissue sections from 151 cases were stained with anti-vimentin, anti-keratin, anti-desmin, anti-S-100 protein, anti-Factor-FVIII released antigen, and anti-lysozyme. Positive staining was obtained in mesenchyme-derived cells, while the epithelial tumor cells did not react with anti-vimentin. It indicated that vimentin antibody is effective for tumor differential diagnosis in surgical pathology.     

上皮钙黏蛋白、波形蛋白和Snail蛋白表型在乳腺浸润性导管癌中表达的相关性及其与预后的关系

目的 检测上皮钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)和Snail蛋白在乳腺浸润性导管癌中的表达情况与乳腺癌病理特征的关系及其与浸润性导管癌预后的关系.方法 采用Envision免疫组织化学方法对89例乳腺浸润性导管癌组织中的上E-cadhenn,Vimentin和Snail蛋白表达情况进行检测并分析表达程度与临床病理特征之间的关系;统计分析采用卡方检验、Fisher精确概率法检验Spearman等级相关检验、配对计数资料检验、Kaplan-Meier法进行单因素生存分析,Cox比例风险模型进行生存的多因素分析.结果 E-cadherin、Vimentin和Snail蛋白在浸润性导管癌组织中的阳性表达率分别为、47.1％、53.9％和55.0％,三者呈负相关,(P=0.003);E-cadherin、Vimentin和Snail蛋白的表达与临床TNM分期有关(P ＜0.005).浸润性导管癌中Snail蛋白、Vimentin表达明显增高,Snail蛋白与淋巴结转移有关(P =0.029);Vimentin与淋巴结转移、雌激素状态有关(P =0.006,P＜0.001);E-cadherin表达明显降低,与孕激素状态有关(P =0.030);分子分型结果显示,管腔A型、HER-2阳性型组的Vimentin、Snail蛋白阳性表达率低于基地细胞样型组(P =0.012),而E-cadherin表达率则高于基地细胞样型组(P =0.004).Cox分析发现,E-cadherin低表达和Vimentin的过度表达与患者总生存期(P =0.019、P=0.045)及患者无病生存期(P =0.032、P=0.024)显著相关,但Snail蛋白的表达与总生存期及无病生存期无相关性(P =0.879、P=0.835).结论 E-cadhern、Vimentin和Snail蛋白在乳腺浸润性导管癌的发生、发展、侵袭及转移中起重要作用,对认识乳腺癌的生物学特性以及对指导乳腺癌的诊疗及预后具有重要意义.     

波形蛋白的结构、功能和与肿瘤的关系

波形蛋白是真核细胞骨架系统的组成成分之一,除了对细胞的黏附、迁移、增殖、凋亡等生理功能起重要作用,同时也与间充质细胞来源的肿瘤分化、转移和增殖以及肿瘤微环境有着密切的关系.文章结合近期有关波形蛋白的研究,综述了波形蛋白结构形态、细胞生物学功能上最新的研究进展以及波形蛋白在肿瘤研究中的相关进展.     

涎腺恶性上皮性肿瘤的诊断和鉴别诊断

发生于涎腺部位的肿瘤较少见,恶性肿瘤更为少见,占所有头颈部恶性肿瘤的5%～6%,仅占全身恶性肿瘤的0.3%。尽管涎腺恶性肿瘤发生率较低,但是它们的形态学变异较大,不同类型的肿瘤之间可有相似的形态学特点,给诊断带来了困难。而不同类型涎腺恶性肿瘤的临床生物学行为迥异,治疗方法也不相同,因而这些肿瘤的明确诊断非常重要。近年来,免疫组化新抗体在涎腺恶性上皮性肿瘤的诊断和鉴别诊断中发挥了重要作用。1正常涎腺组织的免疫组化特点涎腺是管泡状外分泌腺体,由腺泡和导管组成。正常涎腺有2种细胞:腔上皮细胞和非腔上皮细胞。腺泡的腔上皮细…     

恶性黑色素瘤中细胞角蛋白的表达

一、材料和方法１材料：收集本院恶性黑色素瘤（下称恶黑）标本１２例,其中皮肤原发恶黑９例,淋巴结内转移性恶黑３例。无色素性恶黑２例。组织用４％甲醛液固定,石蜡包埋,切片均作ＨＥ染色和细胞角蛋白、波形蛋白、ＨＭＢ４５、Ｓ１００染色。２方法：免疫组化...     

细胞角蛋白7的表达在肿瘤及炎症中的意义

细胞角蛋白(Krt)作为一种中间丝,存在于所有的上皮细胞及部分非上皮细胞.主要作用是维持上皮细胞的机械稳定性和完整性.近年来细胞角蛋白的研究集中在肿瘤的诊断方面,即利用细胞角蛋白在上皮细胞表达的特异性,通过免疫组化技术,运用单克隆抗体进行比对分析,来确定肿瘤的分类、分型或者来源.其中Krt7是一个代表.探讨Krt7的作用,在上皮肿瘤中的分布,以及与细胞角蛋白20(Krt20)在上皮肿瘤中的联合表达情况,对肿瘤的诊断、转移性与原发肿瘤的鉴别等有重要意义.除此之外,Krt7还是一个炎性指标,发挥信号转导中的作用,参与炎症的发生发展,其表达也有利于对某些疾病早期及预后进行监测.     

乳腺癌波形蛋白表达的生物学意义

应用波形蛋白童克隆抗体（Ｖｉｍ）免疫组化ＡＢＣ法对７５例乳腺癌进行标记分析。结果显示，Ｖｉｍ阳性３４例，阳性率４５．３％。统计分析表明，Ｖｉｍ表达与肿瘤的组织学分级有关（Ｐ＜０．００５），Ｖｉｍ阳性肿瘤的ＡｇＮＯＲ均数大于阴性组）Ｐ＜０．０１），Ｖｉｍ阳性组病人的５年生存率低（Ｐ＜０．００５）。以上提示了乳腺癌Ｖｉｍ表达是肿瘤分化低、细胞增生活跃和病人预后不良的指征。     

低度恶性潜能之乳头状尿路上皮肿瘤

世界卫生组织／国际泌尿病理学2004年分类[WHO（2004）／ISUP]对尿路上皮肿瘤分级标准化进行了有益尝试。在乳头状膀胱肿瘤分类中,新加入了“具低度恶性潜能的乳头状尿路上皮肿瘤（PUNLMP）”条目。WHO（2004）／ISUP尿路上皮肿瘤分类系统与被广泛接受的WHO1973年分类相比,具有数项潜在优势：（1）详细定义了不同瘤前病变和不同分级肿瘤的形态标准,包括更加标准化地定义了非浸润性乳头状尿路上皮性肿瘤（NIPUT）的组织学分级标准,有利于提高病理医师间诊断的可重复性;（2）建立了统一的术语和一般性定义;（3）力图将肿瘤分类系统的术语设计得与尿细胞学术语更为吻合,使得细胞-组织学的对应关系更易于操作,为指导改善患者的治疗提供了可能性;（4）去除了模糊的分类级别,如TCC分级Ⅰ～Ⅱ,TCC分级Ⅱ～Ⅲ;（5）单独列出了具有高危险进展为浸润性癌的肿瘤。     

Experimental coexpression of vimentin and keratin intermediate filaments in human melanoma cells augments motility.

Intermediate filaments have been used as cell-type-specific markers in differentiation and pathology; however, recent reports have demonstrated the coexpression of vimentin (a mesenchymal marker) and keratins (epithelial markers) in numerous neoplasms, including melanoma, which has been linked to metastatic disease. To test the hypothesis that coexpression of vimentin and keratins by melanoma cells contributes to a more migratory and invasive phenotype, we co-transfected a vimentin-positive human melanoma cell line, A375P (of low invasive ability), with cDNAs for keratins 8 and 18. The resultant stable transfectants expressed vimentin- and keratin-positive intermediate filaments showed a two- to threefold increase in their invasion of basement membrane matrix and migration through gelatin in vitro. These findings were further corroborated by video cinematography. During attachment and spreading on fibronectin, the transfectants containing vimentin and keratins 8 and 18 demonstrated an increase in focal adhesions that stained positive for beta 1 integrin and phosphotyrosine, along with enhanced membrane ruffling and actin stress fiber formation. From these data, we postulate that coexpression of vimentin and keratins results in increased cytoskeletal interactions at focal contacts within extracellular matrices involving integrin cell signaling events, which contributes to a more migratory behavior.     

Patterns of cytokeratin/vimentin coexpression in the guinea pig

The distribution of cytokeratin and vimentin in guinea pig tissues as seen by immunohistochemistry using monoclonal antibodies is described and a similar distribution pattern of coexpression of cytokeratin and vimentin in various cell types as compared to human tissues were found. The possible explanations for the unusual coexpression of both types of intermediate filaments in normal cells are discussed.     

Spindle cell carcinoma of the renal pelvis. Immunohistochemical and ultrastructural study of a case demonstrating coexpression of keratin and vimentin intermediate filaments

A carcinoma of the renal pelvis characterized histologically by a spindle cell sarcomatoid morphological growth pattern was studied by electron microscopy and immunohistochemical techniques. Ultrastructural examination revealed abundant perinuclear cytoplasmic tonofilament bundles in association with prominent rough endoplasmic reticulum. Immunohistochemical study demonstrated coexpression of keratin and vimentin, two intermediate filaments thought to be specific for epithelial and nonepithelial cells, respectively. It is proposed that the spindle transformation of the epithelial cells in such cases may be explained on the basis of the development by the tumor cells of nonepithelial characteristics, such as the expression of vimentin intermediate filaments, that may be responsible for the adoption of the morphological growth pattern characteristic of neoplasms following mesenchyme-derived lines of differentiation.     

Immunofluorescence staining of keratin filaments in cultured epithelial cells

Summary A procedure is described for the identification of cultured epithelial cells by indirect immunofluorescence staining of keratins. Additionally, some associated techniques such as double staining, keratin antigen unmasking, cytostatic drug treatment and photography are briefly outlined.     

Adenomatoid odontogenic tumour: co-expression of keratin and vimentin

Summary Immunohistochemical observations of intermediate sized proteins in five cases of adenomatoid odontogenic tumour (AOT) are described. The immunohistochemical detections of keratins were made with polyclonal antiserum (TK, 41–65 kDa) and three monoclonal keratin antibodies (KL1: 55–57 kDa; PKK1: 40, 45, and 52.5 kDa and nos. 19, 18, 8; K8.12: nos. 16, 13) and vimentin and desmin monoclonal antibodies. Histologically, the tumour epithelia could be divided into two types: type A cells were a spindle or columnar shape and formed solid, ductal, tubular or whorled structures. Type B cells were small and compact cells at the periphery of the A cell-containing focus. Immunohistochemically, the type A cells showed very slight reaction with all antibodies to keratins, whereas the type B cells indicated slight-to-moderate expression of keratin and vimentin, and showed coexpression. Both types of cell showed a negative reaction for desmin. Only one case was associated with cystic lesions, and the cyst-lining was composed of thin squamous epithelium. Keratin expression in this epithelium was strong. In the histogenesis of AOT it was postulated that the tumour cells may have originated from undifferentiated odontogenic epithelium or stratum intermedium cells.     

Immunofluorescent characterization of fibronectin, laminin, and keratin in normal and neoplastic human mammary epithelial cells in culture and in breast tissue sections

Employing indirect immunofluorescent staining, primary and secondary serum-free cultures and frozen sections of human mammary tissue, normal and neoplastic, were examined for the presence and distribution of fibronectin (FN) and keratin, and frozen sections also for laminin (LM). The epithelial cell purity of the cultures was confirmed by the observation that all cells stained with anti-keratin antibody. In confluent cultures, FN was absent at the apical cell surface, and was seen as a fibrillar matrix exclusively beneath the epithelial monolayer, at the cell-substratum interface. No differences were noted between normal and neoplastic cells in vitro. In sections of normal breast tissue, FN was localized in the basement membrane zone (BMZ) and in the connective tissue stroma. A distinguishing feature of the neoplastic tissue was the considerably more intensive anti-FN immunofluorescence of the stroma. In normal tissue sections, LM was present exclusively in the BMZ, where it formed a continuous, well-delineated, smooth line; this line was found to be distorted, interrupted, and sometimes entirely absent in the neoplastic tissue. The cytoplasm of all cultured cells, neoplastic as well as normal, exhibited a dense network of keratin filaments that was especially prominent around the nucleus. In the sections, keratin was ubiquitously present in the epithelial cells, predominantly along the interior border of the surface membrane; in the neoplastic tissue, this pattern was markedly disorganized, and some of the cells failed to express the substance.     

The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors

Vimentin has been regarded as the intermediate filament characteristic of normal and neoplastic mesenchymal cells and keratins as typical of epithelial cells and the neoplasms derived from them. However, many epithelial cells in tissue culture or in effusion, as well as cells in some solid epithelial neoplasms such as renal, endometrial, ovarian, pulmonary, and thyroid adenocarcinomas, have been shown to coexpress vimentin and keratin. The recent availability of monoclonal antibodies that work reasonably well in paraffin-embedded tissue led us to carry out a comprehensive immunohistochemical study on formalin- and alcohol-fixed specimens of neoplasms in which we used monoclonal antibodies against vimentin. These results were compared with our previous study in which the same tumor tissues were investigated using antibodies against keratin. The antigenicity of vimentin was found to be preserved in all alcohol-fixed specimens and in 63% of formalin-fixed tissues. Vimentin was the sole intermediate filament present in virtually all sarcomas, meningiomas, schwannomas, and melanomas. In addition, variable percentages (10-57%) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas, and mesotheliomas were positive for vimentin, which, except in the neuroblastomas, was coexpressed with keratins. Among the adenocarcinomas, more than 50% of papillary carcinomas of the thyroid, as well as renal, endometrial, ovarian, and lung carcinomas, coexpressed keratins and vimentin. A distinctive paranuclear and basal localization of vimentin was observed in the cells of many of these tumors, in contrast to the predominantly apical distribution of the keratins. The authors conclude that coexpression of vimentin and keratin is more widespread than previously reported and that antibodies to vimentin, by themselves, are of limited value for the differentiation of epithelial from mesenchymal neoplasms.     

Cytokeratin and vimentin expression in normal and neoplastic canine prostate

Intermediate filament expression in the canine prostate, unlike that in human prostate, is represented in the literature by only a few reports. In this study, the expression of cytokeratin (CK) and vimentin was examined in three normal canine prostates and 11 canine prostatic carcinomas. Monoclonal antibodies directed against vimentin, CK AE1/AE3, CK 18-8 (for luminal epithelial cells), CK 5, CK clone 8.12 and CK 14 (for basal cells) were employed. As in man, normal canine prostatic luminal cells were positive for CK 8-18. Basal cells were positive for CK 5 and CK clone 8.12 but, in contrast to findings in man, were negative for CK 14. Luminal cells were vimentin-negative, whereas in man they have been reported as vimentin-positive. The majority of carcinomas showed an undifferentiated histological pattern and all were positive for CK AE1/AE3 and for vimentin. Ten tumours were positive for CK 8-12, but six of them showed many cells co-expressing CK 14. Moreover, in two of these six cases a large number of neoplastic cells also reacted with CK clone 8.12 antibody, and in one of them co-expression of CK 5 was detectable. This co-expression, of luminal and basal cytokeratins, suggests a possible origin of the tumours from prostatic epithelial stem cells. Vimentin expression is an inconstant finding in human prostatic carcinomas; its almost uniform occurrence in canine carcinomas suggests a lesser degree of differentiation than in the human neoplasm.     

Nuclear localization of catechol-O-methyltransferase in neoplastic and nonneoplastic mammary epithelial cells

Catechol-O-methyltransferase (COMT) plays both a regulatory and protective role in catechol homeostasis. It contributes to the regulation of tissue levels of catecholamines and catecholestrogens (CEs) and, by blocking oxidative metabolism of catechols, prevents endogenous and exogenous catechols from becoming a source of potentially mutagenic electrophiles. Evidence implicating CEs in carcinogenesis, in particular in the hamster kidney model of estrogen-induced cancer, has focused attention on the protective role of COMT in estrogen target tissues. We have previously reported that treating hamsters with estrogens causes translocation of COMT to nuclei of epithelial cells in the renal cortex, the site of CE biosynthesis and where the cancers arise. This finding suggested that nuclear COMT may be a marker of a threat to the genome by catechols, including CEs. It is postulated that CEs play a role in the genesis of breast cancer by contributing to a state of chronic oxidative stress that is presumed to underlie the high incidence of this disease in the United States. Therefore, here we used immunocytochemistry to re-examine human breast parenchyma for nuclear COMT. In addition to confirming previous reports of cytoplasmic COMT in mammary epithelial cells, we identified nuclear COMT in foci of mammary epithelial cells in histologically normal breast tissue of virtually all control (macromastia) and cancer patients and in breast cancer cells. There was no correlation between tissue histology and the numbers of cells with nuclear COMT, the size of foci containing such cells, or intensity of nuclear COMT immunostaining. The focal nature of the phenomenon suggests that nuclear COMT does not serve a housekeeping function but that it reflects a protective response to an increased local catechol load, presumably of CEs and, as such, that it may be a characteristic of the population of women studied who share the same major risk factor for developing breast cancer, that of living in the industrialized West.     

Immunohistological recognition of cyclin D1 expression by non‐lymphoid cells among lymphoid neoplastic cells

Cyclin D1 immunostaining of non‐neoplastic cells has been a source of diagnostic confusion especially in lymphoproliferative lesions. This study has reviewed these in two hundred and thirty‐one haematopathological samples stained for cyclin D1. Most cases were formalin‐fixed except for a few bone marrow trephines, which were B‐5 fixed, and EDTA decalcified. Overall, 94% (216/231) of cases showed one or more types of non‐neoplastic cells expressing Cyclin D1 of variable intensity. Endothelial cells and histiocytes were the most commonly identified Cyclin D1 positive cells being positive in 92% (214/231) of cases. Other normal cell types identified included fat cells, stromal fibroblasts, glial cells, spermatocytes, smooth muscle cells, osteoblasts and where present epithelial cells. Many normal cell types can express cyclinD1. Knowledge of these is useful to prevent misinterpretation of cyclin D1 positive tumours.