涎腺肿瘤中肌上皮细胞免疫表型研究

目的:了解p63、Calponin和Caldesmon三种新的肌上皮细胞标记物在涎腺肿瘤中的表达。方法:免疫组织化学S P法检测3 1例涎腺肿瘤(涎腺多形性腺瘤、肌上皮瘤、肌上皮癌、腺样囊性癌和上皮 肌上皮癌)中p63、Calponin和Caldesmon的表达。结果:p63、Calponin和Caldesmon均表达肿瘤中的肌上皮细胞。p63、Calponin和Caldesmon在3 1例涎腺肿瘤中的阳性率分别是93 .6%、77.4%和9.6%。结论:p63、Calponin是涎腺肿瘤中较好的肌上皮细胞标记物,与S 10 0、actin等传统标记物联合应用,更有助于涎腺肿瘤性肌上皮的鉴别诊断。     

组织蛋白酶D在涎腺肿瘤中的表达

为探讨组织蛋白酶Ｄ在涎腺肿瘤中的表达及意义 ,我们对 10 8例涎腺肿瘤中组织蛋白酶Ｄ的表达进行了分析。材料与方法 :涎腺肿瘤标本 10 8例 ,其中粘液表皮样癌40例 ,腺样囊性癌 2 2例 ,腺癌 8例 ,乳头状腺癌 6例 ,肌上皮癌 5例 ,基底细胞腺癌、上皮肌上皮癌和腺泡细胞癌各 4例 ,导管癌 3例 ,恶性多形性腺瘤 2例 ,多形性低度恶性腺癌1例 ,基底细胞腺瘤 7例 ,肌上皮瘤、混合瘤各 1例。采用常规链亲和素三步法进行免疫组织化学染色。设阴性对照并根据染色范围和强度将其分为 (- )、( )、( )和 ( )4个级别。结果 :阳性染色见于涎腺肿瘤…     

涎腺透明细胞肌上皮癌和透明细胞癌的临床病理比较分析

目的：探讨涎腺透明细胞肌上皮癌和透明细胞癌的临床病理与免疫组化特征。方法：回顾分析武汉大学口腔医学院口腔病理科1985～2008年期间确诊的3例透明细胞肌上皮癌和5例透明细胞癌。常规HE染色和免疫组化（CKAE1/AE3,S100,vimentin,smooth muscle actin,calponin,P63和maspin）做比较观察。结果：两种肿瘤几乎全部由透明细胞构成,在透明细胞肌上皮癌中可见少量梭形细胞,透明细胞癌中可见少量含有嗜酸性胞浆的细胞。免疫组化显示：透明细胞肌上皮癌中,3例均阳性表达CKAE1/AE3,S100,vimentin,P63和maspin,2例阳性表达smooth muscle actin和Calponin;透明细胞癌中,5例均阳性表达CKAE1/AE3,P63和maspin,而S100,vimentin,smooth muscle actin,calponin均呈阴性表达。结论：涎腺透明细胞肌上皮癌和透明细胞癌都很罕见,二者可通过组织病理和免疫组化特点进行鉴别。由于肿瘤性肌上皮细胞可呈现不同的肌源性分化,因此联合运用多种提示肌上皮源性的标志物如CKAE1/AE3,S100,vimentin,smooth muscle actin和calponin对二者鉴别诊断有帮助。P63和maspin缺乏特异性。     

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.     

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。     

人和常用实验动物正常涎腺中肌上皮细胞定量组织学研究

目的 了解人与不同实验动物涎腺中肌上皮的细胞的差异。方法 用ＨＨＦ３５对人和动物涎腺进行免疫组织化学染色，用计算机图像分析系统测量肌上皮细胞的平均体积比并进行比较，结果：人和动物涎腺中肌上皮细胞的平均体积比存在不同程度的差异，除啮齿类动物外，人和其它动物粘液腺中肌上皮细胞的平均体积比高于浆液腺中者。结论 涎腺肌上皮细胞的平均体积比与动物种类和涎腺分泌物性能有关。     

人和常用实验动物正常涎腺中肌上皮 细胞定量组织学研究

目的 了解人与不同实验动物涎腺中肌上皮的细胞的差异。方法 用ＨＨＦ３５对人和动物涎腺进行免疫组织化学染色，用计算机图像分析系统测量肌上皮细胞的平均体积比并进行比较，结果：人和动物涎腺中肌上皮细胞的平均体积比存在不同程度的差异，除啮齿类动物外，人和其它动物粘液腺中肌上皮细胞的平均体积比高于浆液腺中。结论 涎腺肌上皮细胞的平均体积比与动物种类和涎腺分泌物性能有关。     

许旺细胞标记物GFAP与肌上皮细胞标记物α-SMA在涎腺腺样囊性癌中共表达

目的 检测许旺细胞标记物胶原原纤维酸性蛋白（GFAP）与肌上皮细胞标记物α-平滑肌肌动蛋白（d-SMA）在涎腺腺样囊性癌（ACC）中的表达情况，并探讨GFAP、α-SMA与ACC嗜神经侵袭的关系。方法 用免疫组织化学、免疫荧光双标记及激光共聚焦显微镜技术检测GFAP蛋白与α-SMA蛋白在ACC组织中的表达。结果 在ACC组织中，GFAP蛋白与α-SMA蛋白均有表达，二者在同一肿瘤性肌上皮样细胞胞质中共表达。结论 ACC中肿瘤性肌上皮样细胞发生许旺细胞分化并侵袭神经可能是ACC嗜神经侵袭的组织病理学基础。     

粘液表皮样癌组织发生的免疫组织化学研究

为探讨涎腺液表皮样癌的组织发生,本文采用三种特异性抗体:上皮肤抗原(EMA);肌动蛋白(actin);波形蛋白(vimentin)对25例涎腺粘液表皮样癌进行免疫组织化学研究。结果发现,粘液表皮样癌中三种肿瘤细胞对EMA反应阳性,部分表皮样细胞和中间细胞对actin和Vimentin反应阳性,粘液细胞反应阴性。研究结果表明,粘波表皮样癌是上皮源性的肿瘤,其中表皮样细胞和中间细胞具有肌上皮细胞的分化特征。提示,肿瘤性腺上皮与肿瘤性肌上皮细胞同时参与了该肿瘤的组织发生。     

MUC-1 expression in pleomorphic adenomas using two human milk fat globule protein membrane antibodies (HMFG-1 and HMFG-2)

Pleomorphic adenoma (PA) is the most common salivary gland tumor and its microscopic features and histogenesis are a matter of debate. Human milk fat globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland tumors.

Objective

The aim of this study was to assess the immunoexpression of the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs, contrasting these results with those from normal salivary gland tissue.

Material and Methods

Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG-2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin method was used.

Results

Positivity to HMFG-1 and HMFG-2 MoAbs was found in ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls and intraductal mucous material. Two kinds of myoepithelial cells were identified: classic myoepithelial cells around ducts were negative to both MoAbs, and modified myoepithelial cells were positive to both MoAbs. This last cellular group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal epithelial cells using both HMFG antibodies. Intraductal mucous secretion was also HMFG-1 and HMFG-2 positive.

Conclusions

Our results showed there are two kinds of myoepithelial cells in PA. The first cellular group is represented by the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The second one is HMFG-negative and represented by the neoplastic myoepithelial cells located around the ducts.     

Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors

The organization of salivary gland ducts, especially the presence or absence of myoepithelial cells, is central to histogenetic approaches to the classification of salivary gland tumors. Striated and excretory ducts are reported to be devoid of myoepithelial cells but do contain basal cells. To investigate the nature of such basal cells, tissue sections of normal human salivary glands were examined by means of immunohistochemical, ultrastructural, and fluorescent microscopic techniques. With the use of a mouse monoclonal anticytokeratin antibody (3 12C8-1) that, in salivary glands, is specific for myoepithelial cells, these cells associated with acini and intercalated ducts were strongly stained, as were the basal cells of striated and excretory ducts in each case. Ultrastructurally, some basal cells of both striated and excretory ducts had narrow, elongated cellular processes or the main portion of the cell containing parallel arrays of microfilaments with linear densities and micropinocytotic vesicles, whereas in other basal cells tonofilament bundles predominated. A similar range of cytoplasmic features existed in myoepithelial cells associated with acinar and intercalated duct cells. In addition, some duct basal cells have a complement of actin filaments similar to classic myoepithelium of acini and intercalated ducts. Striated and excretory ducts of human salivary glands, therefore, contain fully differentiated and modified myoepithelial cells, both of which express a specific cytokeratin polypeptide that is absent from duct luminal and acinar cells. Differentiation patterns in the intralobular and interlobular ducts suggest that these regions of salivary gland parenchyma cannot be excluded as histogenetic sites for the induction of salivary gland tumors in which neoplastic myoepithelial cells have been shown to have a major role.     

Histologic evaluation of myoepithelial participation in salivary gland tumors

To evaluate the myoepithelial participation in various salivary gland tumors, 40 cases were studied using the tannic acid--phosphomolybdic acid--Levanol fast cyanine 5RN (TPL) method directly correlated with ultrastructural observation. The TPL positivity corresponded to cytofilaments, especially microfilaments within the cells showing myoepithelial features. This approach allowed categorization of the examined tumor types into the following 4 groups according to the degree of myoepithelial participation: tumors with major myoepithelial, epithelial-myoepithelial (biphasic), minor myoepithelial, and no myoepithelial participation. It is suggested that the first 2 categories form a spectrum with myoepithelioma and basal cell adenoma at the extremes, in which neoplastic myoepithelial cells assume an active and integral constitutive r?le. The present findings indicate that the TPL method offers a very reliable marker for the screening of neoplastic myoepithelium in salivary gland tumors and thus may help in subclassification on a histogenetic basis for these tumors.     

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.     

HLA-DR antigens in normal, inflammatory, and neoplastic salivary glands

A monoclonal antibody to HLA-DR antigens that is reactive in formalin-fixed tissues was used with the immunoperoxidase method to evaluate 212 salivary gland lesions (normal, nonspecific, and autoimmune inflammatory, benign, and malignant tumors). Results of immunostaining showed that (1) intercalated ducts, myoepithelial cells, and acinous cells of normal salivary glands express HLA-DR antigens, (2) autoimmune salivary gland disease results in greater HLA-DR expression than that seen in nonspecific inflammatory lesions or normal glands, (3) stromal cells associated with benign and malignant salivary gland tumors express HLA-DR antigens, and (4) numerous benign and malignant salivary gland tumors express HLA-DR antigens. It was of interest that lymphocyte-rich Warthin's tumors displayed epithelial immunoreactivity, whereas oncocytomas devoid of a lymphocytic component were invariably negative. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is both a normal and an inducible phenomenon in salivary glands, salivary gland neoplasia, and the desmoplastic host response. There is no discriminatory role in the immunologic detection of HLA-DR for differential diagnosis of salivary gland tumors.     

涎腺肿瘤中的肌上皮细胞标志物

涎腺肿瘤中具有肌上皮分化的占大部分,而肌上皮细胞及其变异型在常规切片中难以辨认,常需要免疫组织化学给予鉴别.因此,肌上皮细胞的免疫组织化学标志物成为研究的热点.本文就近几年来涎腺肿瘤肌上皮细胞的免疫组织化学标志物研究进展作一综述.     

Distribution of intermediate filaments in the salivary glands and salivary gland tumors]

13 cases of salivary glands and 30 of salivary gland tumors were studied by ABC method with 6 monoclonal antibodies to intermediate filaments and one to microfilament. The results showed that the distribution of intermediate filaments in salivary glands had their regularity. According to the reaction to the antibodies, these tumors could be divided into 3 groups and 3 subgroups. The findings also suggested that in the salivary gland tissue the epithelial cells which mainly contained the 54 Kd keratin and the epithelial cells which mainly contained 57/66 Kd keratin were the origin of the salivary gland tumors. The actin-positive myoepithelial cells might play a role in some tumor formation.     

Assessment of p63 expression in the salivary gland neoplasms adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, and basal cell and canalicular adenomas

PURPOSE: The purpose of this study was to determine the extent of p63 immunoreactivity in the malignant salivary gland neoplasms adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA) and to compare this to the expression of this marker in the benign salivary gland tumors canalicular adenoma and basal cell adenoma. Few studies on the expression of p63 in head and neck salivary gland tumors have been published to date. P63, a selective immunohistochemical marker of basal/stem cells of stratified epithelium and of myoepithelial cells, is a p53 homologue that plays an essential role in both morphogenesis of epidermis and limb development. P63 immunoreactivity has been demonstrated in squamous cell and urothelial carcinomas. It is generally absent in most nonsquamous cell carcinomas.Study design Formalin-fixed paraffin-embedded sections from 49 salivary gland neoplasms, representing 6 canalicular adenomas, 11 basal cell adenomas, 17 PLGA and 15 ACC accessioned from 1989 to 2002 by the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, NY, were stained with an anti-p63 monoclonal antibody. RESULTS: Nuclear p63 reactivity was uniformly positive in PLGA (17/17, 100%). Positive reactivity was also identified in the majority of cases of ACC (13/15, 87%), primarily in the nonluminal myoepithelial-like cells surrounding luminal cells. Canalicular adenoma did not exhibit any p63 immunoreactivity. All basal cell adenomas of parotid origin stained strongly for p63, with staining localized to the peripheral tumor cells situated adjacent to the connective tissue stroma. None of the basal cell adenomas originating in the upper lip stained with p63. In native adjacent salivary gland tissue, p63 reactivity was identified focally in the nuclei of myoepithelial and basal duct cells. CONCLUSIONS: P63 is strongly expressed in basal cell adenoma of parotid origin, and in ACC and PLGA. Canalicular adenoma did not demonstrate p63 staining, consistent with this tumor's putative luminal ductal cell differentiation. Our results suggest that the neoplastic cells in PLGA may represent either a population of p63-positive epithelial stem/reserve cells similar to the basal cells of stratified epithelium, or modified myoepithelial cells. Given the staining pattern of the tumors examined, p63 does not appear to be an ideal marker for distinguishing between ACC, PLGA, and basal cell adenoma.     

Maspin expression in normal and neoplastic salivary gland

BACKGROUND: Maspin inhibits cell motility, invasion and metastasis. Loss or reduction in maspin expression has been associated with tumoral progression. METHODS: The presence of maspin was studied immunohistochemically in salivary gland tumours presenting cells with myoepithelial differentiation in their composition, and in normal salivary gland. RESULTS: Pleomorphic adenoma (PA) presented high expression of maspin, except in the spindle cells and occasional luminal cells. Epithelial-myoepithelial carcinoma and tubular adenoid cystic carcinoma (ACC) showed intense expression in all cells. Cribriform ACC evidenced only few positive cells of the luminal type, while solid subtype showed rare positive cells. Normal salivary gland tissue has shown low levels of maspin positivity. CONCLUSIONS: Maspin has small participation in normal salivary gland, is increased in PA, and decreases as the histological malignancy raises. Hence, in salivary gland, its expression is not exclusive of myoepithelial cells; thus, it should not be used as a marker for this cell. Nevertheless, we believe it is an important marker of biological behaviour in these tumours.