涎腺粘液表皮样癌免疫组化研究

应用癌胚抗原(CEA)、角蛋白(Keratin)及上皮细胞膜抗原(EMA)免疫组织化学,对19例粘液表皮样癌进行了免疫定位观察.结果发现:正常涎腺组织CEA阴性,癌旁正常涎腺组织弱阳性。Keratin导管阳性,部分肌上皮细胞阳性。EMA导管阳性,腺泡阴性。粘液表皮样癌肿瘤组织阳性率CEA 78.9％,Keratin89.5％,EMA 84.2％。同时发现CEA、EMA随着肿瘤的分化降低而减弱,Keratin则无明显变化。     

涎腺粘液表皮样癌的免疫组织化学研究

本文就涎腺粘液表皮样癌的组织发生,采用免疫组织化学手段,例如中丝蛋白、S—100蛋白、癌胚抗原、肌凝蛋白、肌动蛋白、上皮膜抗原等进行研究。结果提示涎腺粘液表皮样癌可能来源于涎腺导管储备细胞或肌上皮细胞。     

纤维凝集素在涎腺上皮性肿瘤中定位的免疫组织化学研究

用纤维凝集素抗血清,对32例涎腺肿瘤进行免疫组织化学(ABC 法)研究,旨在探讨这些肿瘤的结构性质及其组织发生。结果如下:1.多形性腺瘤中,部分肿瘤细胞结构周围有基底膜样 FN 环绕。部分肿瘤细胞结构周围有 FN 阳性细胞,且增殖,并和肌上皮片块、粘液软骨样区相延续。2.腺样囊性癌中,FN 在筛孔状结构呈围腔状分布,筛孔周围细胞为肿瘤性肌上皮细胞。3.腺淋巴瘤、基底细胞睬瘤、粘液表皮样癌、腺泡细胞癌中的肿瘤上皮结构周围基底膜区,FN呈线状环绕,表明这些肿瘤中不含肌上皮细胞,肿瘤细胞仅发生了腺上皮或鳞状上皮分化。4.各涎腺肿瘤中,肿瘤性上皮结构周围基底膜区和间质中 FN 分布的多寡和方式不同。     

表皮生长因子受体在涎腺肿瘤中的表达

采用单克隆抗表皮生长因子受体(EGFR)抗体,用免疫组化的方法,对44例涎腺肿瘤进行 EGFR检测。EGFR 的表达方式分两类:大多数为胞紧或胞膜阳性,少数为胞核阳性。阳性细胞分布于:导管上皮,特别是形成腺管样结构的腔面细胞;部分肌上皮细胞,特别是浆样肌上皮;鳞状细胞,包括鳞状细胞癌细胞、粘液表皮样癌的表皮样细胞以及多形性腺瘤中鳞状化生的瘤细胞;Warthin 氏瘤的上皮细胞;以及基底细胞腺瘤中部分基底样细胞。EGFR 在涎腺肿瘤中的阳性表达,既不能作为细胞增殖活跃的依据,也不能作为判断肿瘤良恶性的指标。     

涎腺粘液表皮样癌的治疗及预后

粘液表皮样癌来源于涎腺导管上皮 ,在涎腺恶性肿瘤中比较多见 ,约占所有涎腺肿瘤的 10 % ,涎腺恶性肿瘤的30 %。病理上可分为高度恶性及低度恶性二类。组织学上以含有粘液细胞、表皮样细胞和中间型细胞为特征 ,有时还可见到透明细胞及嗜酸细胞。高分化者粘液细胞及表皮样细胞较多 ,中间细胞少 ;低分化者主要为表皮样细胞和中间细胞 ,而粘液细胞少。许多文献报道 ,粘液表皮样癌的预后与肿瘤的病理学分型密切相关 ,低分化型粘液表皮样癌侵袭性强 ,转移率高 ,并可发生远处转移[1] 。粘液表皮样癌的治疗目前仍主要以传统的手术、放疗和化疗为主 …     

涎腺多形性腺瘤的组织发生学研究——用免疫组化法看多形性腺瘤

本文用自制的角蛋白和S-100蛋白抗体、细胞性角蛋白(低分子量)和波形丝蛋白单克隆抗体,对26例涎隙多形性腺瘤进行了PAP法免疫组化研究,结果显示:导管样结构的内层细胞、鳞状化生区、肌上皮片块及粘液样组织的部分细胞以及软骨样陷窝的周边均呈角蛋白阳性,导管样结构的外层细胞、肌上皮片块和粘液样组织及软骨样细胞均呈S-100蛋白阳性,波形丝蛋白在肌上皮片块及粘液软骨样结构的部分细胞呈阳性。本文将这些结果与正常涎腺的免疫组化结果相对比,经分析讨论得出:多形性腺瘤的组织发生主要与导管上皮有关。肿瘤内的肌上皮样细胞可能为固有肌上皮细胞的异常增殖分化,也可能为导管上皮在病变时化生而来,而粘液,软骨样结构主要为导管上皮通过肌上皮细胞的多向分化、形成所致。上皮细胞在发生肿瘤化时,其内的角蛋白抗原可能也同时发生着某种规律性的变化。了解这点,对进一步认识和研究涎腺上皮性肿瘤有重要意义。     

涎腺粘液表皮样癌中癌胚抗原的免疫组织化学初步观察

本研究用癌胚抗原的多克隆抗体,ABC法对12例涎腺粘液表皮样癌进行了癌胚抗原定位研究。结果表明:所有标本中均显示有癌胚抗原的存在,主要分布在粘液细胞、表皮样细胞及导管上皮细胞。中间细胞未见阳性染色反应。     

涎腺肿瘤中Pax9基因的表达及其意义

目的:检测正常涎腺组织及涎腺肿瘤中转录因子Pax9的表达。方法:采用免疫组化SABC法,研究Pax9在正常涎腺组织、多形性腺瘤、腺淋巴瘤、基底细胞腺瘤、粘液表皮样癌和腺样囊性癌共48例中的表达情况。结果:除1例多形性腺瘤外,其余组织均表达Pax9。正常涎腺的腺泡细胞和导管内衬细胞、多形性腺瘤的上皮细胞、腺淋巴瘤的肿瘤上皮细胞和基底细胞腺瘤中Pax9弱阳性表达,差异没有显著性;而在增殖活跃的细胞如正常涎腺导管的基底细胞和恶性肿瘤细胞(粘液表皮样癌、腺样囊性癌)中表达增强,恶性肿瘤中Pax9的强阳性表达率明显增高,与正常和良性肿瘤相比具有显著差异(P<0.05)。结论:Pax9在涎腺肿瘤尤其是恶性肿瘤的发生过程中发挥重要的作用。     

涎腺粘液表皮样癌光镜、电镜及免疫组织化学的研究

光镜研究表明粘液表皮样癌由三种基本细胞所组成,即粘液样细胞、表皮样细胞及中间细胞。比较一致地认为该瘤起源于涎腺的大导管。近年来随着电镜和免疫组织化学技术的应用,发现了肿瘤中肌上皮样细胞的存在,因而,“闰管”或“闰管-腺泡”单位起源的新学说被提出。本文详细介绍了粘液表皮样癌的临床组织学分型问题。     

涎腺正常与肿瘤组织中p63、CK5、CK19、CEA及SmA的表达

目的:探索涎腺正常导管、腺泡及其上皮性肿瘤的组织起源.方法:采用免疫组化(二步法)检测正常涎腺组织14 例、多形性腺瘤14 例、基底细胞腺瘤8 例、腺样囊性癌18 例、黏液表皮样癌9 例、低分化腺癌2 例及腺泡细胞癌、乳头状腺癌、恶性多形性腺瘤、肌上皮癌各1 例中p63、CK5、CK19、CEA及SmA的表达.结果:正常涎腺基底细胞与肌上皮细胞层表达CK5,其中部分细胞表达p63,导管部分基底细胞也呈CK19阳性.多形性腺瘤、基底细胞腺瘤、腺样囊性癌与黏液表皮样癌具p63、CK5及CK19高阳性率, SmA阳性率分别为85.71%、1.25%、61.11%、0.00%.CEA阳性细胞见于11.11%腺样囊性癌与55.56%黏液表皮样癌.结论:正常涎腺导管和腺泡的腺上皮及涎腺上皮性肿瘤可能来源于导管、腺泡基底层内呈p63和CK5阳性细胞中的干细胞.     

Immunohistochemical and fluorescent microscopic study of histogenesis of salivary mucoepidermoid carcinoma

The purpose of the present investigation was to study the histogenesis of the mucoepidermoid carcinoma of the salivary glands. Eleven cases of mucoepidermoid carcinoma of the minor salivary glands and five of the major glands were extensively studied employing immunohistochemical and fluorescent microscopic techniques. Both the intermediate cells and the duct cells showed a rather similar pattern of reactivity for vimentin, actin and EMA. Also, the intermediate cells and the myoepithelial cells showed a similar reaction pattern for keratin and UGA-1. The intermediate, myoepithelial and duct cells shared a similar reaction pattern for desmin, myosin, CEA, and S-100 protein. However, the rest of the tumor markers studied (AFP, PNA and WGA) were found to be non contributary. We also found that the intermediate and to some extent the epidermoid tumor cells showed a positive reaction with Azophloxine GA, which is a selective stain for myoepithelial cells in the normal glands. Based on these findings, the duct cells, the myoepithelial cell in the normal glands and the intermediate cells of the mucoepidermoid carcinoma share certain similar characteristics. The intermediate cells may actually be a mixed population, some having characteristics of the myopithelial cells and others of duct cells. These findings are relevant to the possible role of the intermediate cell in the histogenesis of the mucoepidermoid carcinoma.     

Ultrastructural and immunohistochemical observations of a true malignant mixed tumor (carcinosarcoma) of the tongue

True malignant mixed tumor (TMMT) of salivary glands, with both carcinomatous and sarcomatous components, is exceedingly rare. We offer a case of TMMT in a 79-yr-old man, which may represent the first report example of this unusual neoplasm arising in the tongue. The carcinomatous component was mainly of solid basaloid carcinoma with focal glandular differentiation, while the sarcomatous component was composed of pleomorphic elements such as chondrosarcoma, myxosarcoma and fibrosarcoma. Carcinoma cells at the periphery of solid nests occasionally merged into these sarcomatous elements. Immunohistochemically, basaloid carcinoma cells showed positive reaction for both low molecular weight cytokeratin and S-100 protein, whereas carcinoma cells lining ductal spaces were positive for a wide spectrum of keratin and EMA. The sarcomatous elements revealed the presence of vimentin and S-100 protein. Ultrastructurally, basal lamina-like material and/or mucoid precipitates often accumulated separating the tumor cells from each other singly or into a few cell group. Some sarcomatous cells assumed the myoepithelial features, such as the presence of microfilament bundles with dense bodies and pinocytotic vesicles along the cell periphery. These findings may indicate that TMMT shares a common histogenesis with pleomorphic adenoma.     

Expression of smooth-muscle actin in cultured cells from human plasmacytoid myoepithelioma

Objective. The definition of plasmacytoid myoepithelioma, a neoplasm exhibiting myoepithelial differentiation, has been recently questioned. To better understand the histogenesis of this neoplasm, we searched for myoepithelial markers in histologic sections of plasmacytoid myoepithelioma and in a cell line (M1) derived from this same neoplasm.Study design. Expression of vimentin, pan-keratin (AE-3) and smooth-muscle actin was studied by immunohistochemistry in paraffin-embedded tissue and by immunofluorescence in M1 cells.Results. Plasmacytoid myoepithelioma tumor sections showed vimentin and AE-3 reactivity, but evidence of smooth-muscle actin was not seen. The cell line derived from this tumor also produced vimentin and cytokeratin. In addition, all cultured cells expressed smooth-muscle actin.Conclusion. We demonstrated that cells derived from a case of plasmacytoid myoepithelioma appear to show full myoepithelial differentiation in vitro. Thus, they are myoepithelial-like cells in nature. The lack of myogenous differentiation in vivo could be due to an inhibitory process mediated by the extracellular matrix.     

Malignant myoepithelial carcinoma (myoepithelioma) arising in a pleomorphic adenoma of the parotid gland. An immunohistochemical study and review of the literature

A 66-year-old woman presented with a giant tumor of the parotid gland, which under a light microscope had a sarcomatous appearance with spindle-shaped myoepithelial cells (malignant myoepithelioma). Histochemical examination showed longitudinal fibrils in the cytoplasm of the myoepithelial cells. Immunohistochemical studies showed positive staining for S-100 protein, vimentin, and actin in the myoepithelial cells. Cytokeratin was seen in the ductular epithelial cells and in the periductular myoepithelial cells, but it was absent from malignant myoepithelial cells. Ultrastructurally, these cells contained several longitudinally oriented slender structures resembling myofilaments without dense bodies. A review of the literature confirms the rarity of malignant myoepithelial carcinoma (myoepithelioma) arising in the parotid gland, and we therefore add another case.     

Actin versus vimentin in myoepithelial cells of salivary gland tumors: A comparative study

Vimentin versus actin expression was immunohistochemically studied in myoepithelial cells of 24 salivary gland tumors in which the participation of myoepithelial cells as a tumoral component has been postulated: two basal cell adenomas, seven pleomorphic adenomas, two myoepitheliomas, seven adenoid cystic carcinomas (two tubular, four cribriform, one solid), six polimorphous low-grade adenocarcinomas. Immunostaining was carried out in formalin-fixed tissue serial sections (3 μm) by the avidin-biotin method, using the antibody vimentin (Dako Corp., Carpenteria, Calif.) and the antibody HHF35 anti-muscle actin (Enzo Biochemical, N.Y.). Our results have confirmed positive staining for vimentin in all salivary tumors studied, although in some tumors it was only in focal areas. The staining for the HHF35 antibody to muscle actin was only consistently found in the adenoid cystic carcinomas of the tubular and cribriform patterns. This study suggests that actin is at least somewhat replaced by vimentin in neoplastic tumoral cells. Therefore vimentin can be used to define the participation and distribution of myoepithelial cells in these tumors.     

Ultrastructural study of the histogenesis of salivary gland mucoepidermoid carcinoma

This electronmicroscope study of the histogenesis of mucoepidermoid carcinoma is based on 15 cases from the major and minor salivary glands. Six major cell types were identified: undifferentiated (cuboid) stem cells, intermediate (columnar) cells, serous/mucoid secretory cells, mucus-producing goblet cells, squamous/epidermoid cells and myoepithelium. It is proposed that undifferentiated stem cells serve as pluripotential reserves which give rise to the various cell types seen in mucoepidermoid carcinoma. Reserve cells in the acinar-intercalated duct components of the salivary glands appeared to give rise to the serous/mucoid and myoepithelial cell populations of mucoepidermoid carcinoma. Reserve cells in the proximal ducts system (intra/extralobular striated ducts and excretory ducts) differentiated into myoepithelium, intermediate (columnar) cells, squamous/epidermoid and mucus-producing goblet cell lines. It is proposed that neoplastic reserve cells give rise to different tumor types in the salivary glands. These types result from varying admixtures and arrangements of tumor cells at different stages of their structural and functional cytodifferentiation from reserve cells. It is further proposed that neoplastic reserve cells differentiate along similar cell lines as the embryonic "stem cells" in the development of normal salivary glands.     

Immunohistochemical localization of CEA,EMA and keratin in salivary mucoepidermal carcinoma]

Localizations of CEA,EMA and keration in 19 cases of mucoepidermal carcinomas were investigated using the indirect immunoperoxidase technique.The results showed CEA was negative in normal salivary glands and showed faint reaction in glands near carcinoma tissue.Keratin and EMA were localized in some myoepithelial cells.The positive rates in carcinoma tissue were 78.9%,89.5% and 84.2%,respectively.The positive rates and staining intensity of CEA and EMA in carcinoma tissue gradually decreased with the decline of tumor differentitation,but that of keratin showed no variation.the author consider that CEA and EMA could become good indices in clinically diagnosing mucoepithelial carcinoma and determining tumor differentiation type cell in mucoepidermal carcinoma and have a potential to multiply express the tumor elements of epithelium and/or mesenchyma.     

Coexpression of keratin and vimentin in salivary pleomorphic adenomas

The coexpression of keratin and vimentin is described in 45 pleomorphic adenomas using an immunoperoxidase MAb method. Histopathologically, the outer layer of tubuloductal structures and peripheral tumor cells in solid masses, including modified or neoplastic myoepithelial cells, showed positive staining with monoclonal keratin antibody K8.12 and vimentin. This staining was found in the ratio of 10/26 (38.5%) in tubuloductal structures, 2/7 (28.6%) in peripheral tumor cells and 8/12 (66.7%) in modified myoepithelial cells. Concomitant staining of other keratin antibodies (PKK1, KL1) and vimentin did not exist. In addition, the ductal basal cells of normal salivary glands showed positive K8.12 labelling. The histogenesis of pleomorphic adenoma is discussed in relation to the differentiation of either ductal basal cells or ductal luminal cells from a single stem cell origin or the direct transformation of ductal basal cells to outer tumor cells and/or modified myoepithelial cells, both coexpressing K8.12 and vimentin.     

Expression of PLUNC family members in benign and malignant salivary gland tumours

Objectives: The aim of this study was to determine the expression of PLUNC proteins in benign and malignant salivary gland tumours and thus their potential use as diagnostic and / or prognostic tools. Materials and methods: A tissue microarray was assembled from 64 salivary gland tumours including adenoid cystic carcinoma, carcinoma ex‐pleomorphic adenoma, mucoepidermoid carcinoma, polymorphous low‐grade adenocarcinoma, pleomorphic adenoma, acinic cell carcinoma, myoepithelial carcinoma and papillary cystadenocarcinoma. Clinicopathological data were collected retrospectively and immunohistochemical analysis of three PLUNC proteins (SPLUNC1, SPLUNC2 and LPLUNC1) was performed. Immunoreactivity was assessed as positive or negative. Results: PLUNC expression was only found in mucoepidermoid carcinomas and papillary cystadenocarcinoma; all other tumours studied were negative. Mucin plugs, mucous and intermediate cells of mucoepidermoid carcinomas were positive for LPLUNC1 and SPLUNC2, but areas composed of epidermoid and clear cells were negative for all PLUNCs. Papillary cystadenocarcinoma was positive for all PLUNCs. No correlation was found with tumour grade or outcome. Conclusions: Intense expression of two PLUNC proteins in mucous cells and mucin plugs of mucoepidermoid carcinoma and papillary cystadenocarcinoma indicate that they could be used as additional diagnostic tools in some equivocal cases, but further studies are needed to understand the biological processes involved in PLUNC expression.     

金属硫因蛋白在涎腺肿瘤中的表达及意义

为了研究金属硫因蛋白在涎腺肿瘤中的表达特点，作者用免疫组织化学方法对７５例涎腺肿瘤进行了研究。在腺上皮和肌上皮混合构成的肿瘤，如：腺样囊性癌、多形性腺瘤、腺上皮肌上皮癌、基底细胞腺瘤（癌）等，金属硫因蛋白只在肌上皮细胞中表达并且均有较强染色。肌上皮癌和肌上皮瘤中有相当多的细胞表达金属硫因蛋白。抗金属硫因蛋白单克隆抗体对肌上皮细胞的染色在部分病例较Ｓ－１００蛋白和平滑肌动蛋白效果好。本结果表明，金属硫因蛋白可能成为涎腺肿瘤性肌上皮细胞较好的标志，有助于涎腺肿瘤的鉴别诊断。