细胞外基质金属蛋白酶诱导因子表达与唾液腺肿瘤侵袭性的关系

目的:检测唾液腺肿瘤组织中细胞外基质金属蛋白酶诱导因子(EMMPRIN)的表达和定位,探讨其与唾液腺肿瘤侵袭性生物学行为的关系。方法:采用免疫组织化学方法,检测9例唾液腺正常组织、28例多形性腺瘤(PA)、25例黏液表皮样癌(MC)、33例腺样囊性癌(ACC)中EMMPRIN的表达和定位。采用SPSS10.0软件包进行多个样本率间的χ2检验或确切概率分析。结果:EMMPRIN在正常唾液腺组织、多形性腺瘤、黏液表皮样癌、腺样囊性癌的表达阳性率分别为11.11%、53.71%、84.00%和90.91%(P<0.05)。在正常唾液腺组织的表达主要见于导管上皮细胞的细胞膜;EMMPRIN蛋白在多形性腺瘤、黏液表皮样癌、腺样囊性癌的表达见于肿瘤细胞的胞膜或胞质。腺样囊性癌嗜神经现象组中,EMMPRIN表达的阳性率高于无嗜神经现象组,但差异无统计学意义。结论:EMMPRIN的表达与唾液腺肿瘤侵袭性生物学行为密切相关。     

腺样囊性癌中细胞外基质金属蛋白酶诱导因子的表达和微血管密度检测

目的:检测腺样囊性癌中细胞外基质金属蛋白酶诱导因子(Extracellular matrix metalloproteinase inducer,EMMPRIN)的表达和微血管密度(Microvessel density,MVD),探讨EMMPRIN和MVD在腺样囊性癌侵袭性方面的生物学作用机理.方法:用SP免疫组化法检测28例多形性腺瘤,33例腺样囊性癌中EMMPRIN的表达和MVD值.采用SPSS 10.0统计软件进行两样本间率的χ2检验和两组之间样本均数的t检验.结果:EMMPRIN在多形性腺瘤、腺样囊性癌的表达阳性率分别为53.71%、90.91%(P＜0.05).腺样囊性癌的MVD值高于多形性腺瘤.腺样囊性癌嗜神经现象组中EMMPRIN表达的阳性率和MVD值高于无嗜神经现象组,但差异不具有统计学意义.结论:EMMPRIN的表达和微血管密度与腺样囊性癌侵袭性的生物学行为密切相关.     

舌鳞癌组织细胞外基质金属蛋白酶诱导因子的表达及其与预后的关系

目的：研究舌鳞癌组织中细胞外基质金属蛋白酶诱导因子（EMMPRIN）的表达及其与舌癌患者临床病理特征和生存期之间的相关性。方法：应用SP免疫组织化学法,检测68例舌鳞癌组织及相应的癌旁组织中EMMPRIN的表达情况,并对68例舌鳞癌患者进行随访观察。应用非参数秩和检验检测两个独立样本的EMMPRIN的表达差异,应用SPSS 13.0软件包进行生存分析;应用Cox比例风险模型分析预后。结果：EMMPRIN在舌鳞癌组织中的表达阳性率高于相应的癌旁组织（P〈0.05）。舌鳞癌组织中EMMPRIN的表达与肿瘤大小和临床分期密切相关,与性别、年龄、淋巴结转移和肿瘤病理分化程度不相关。Cox比例风险模型多因素预后分析显示,EMMPRIN表达是影响舌鳞癌患者预后的独立因素。结论：EMMPRIN可以作为舌鳞癌预后判断的参考指标,并有望成为口腔癌生物治疗的潜在靶点。     

A study of the extracellular matrix in salivary gland tumors

BACKGROUND: Epithelial-mesenchymal interactions constitute fundamental phenomena in the development and maintenance of the characteristic branching pattern seen in salivary glands. This study was undertaken to discuss the extracellular matrix (ECM) role in morphogenesis and cellular differentiation of salivary gland tumors originating from the intercalated duct. METHODS: The ECM components, laminin (LN), type IV collagen, fibronectin (FN), and tenascin (TN) were revealed using a streptoavidin-biotin immunohistochemical technique and analyzed in 34 cases of salivary gland tumors: pleomorphic adenoma (PA); myoepithelioma; basal cell adenoma (BCA); polymorphous low grade adenocarcinoma (PLGA); and adenoid cystic carcinoma (ACC). RESULTS: LN and type IV collagen were present in all tumors, confining well-organized duct-like structures, separating them from the stroma, or surrounding cell clusters. In PA and myoepithelioma, the basement membrane (BM) fragmentation was observed through LN and type IV collagen staining around each individual spindle-shaped cell, which was strictly related to the cell modification. Interestingly, BM interruption could not be seen in the malign tumors, however, was frequently augmented in some cases. LN, type IV collagen, and FN were also found in the stroma of all tumors studied, except for the pseudocystic spaces of ACC, which were only delimited by replicated LN and type IV collagen. TN exhibited a variable expression, being more intense in solid ACC. CONCLUSIONS: LN and type IV collagen were always present around morphologically well-differentiated duct-like structures in all tumors studied. BM interruption could not be seen in the malign tumors, on the contrary BM production was evident, which is probably related to invasion. FN was present in the stroma of all tumors, but TN was mostly observed in less differentiated and higher degree of malignancy tumors, such as solid ACC.     

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。     

Hyaluronan and CD44 expression in minor salivary gland tumors

OBJECTIVES: Hyaluronan (HA) and CD44 are most likely associated with tumor invasion and metastasis. Malignancies with different degrees of aggressiveness may express different levels and patterns of HA and CD44. The aim of this project was to examine the distribution of HA and CD44 in minor salivary gland tumors to determine if staining could be correlated with biologic behavior or tumor type. MATERIALS AND METHODS: Biotinylated hyaluronan binding protein as a probe for HA and monoclonal antibodies specific for CD44 were used to stain classic examples of the five most commonly encountered minor salivary gland tumors: monomorphic adenomas, pleomorphic adenomas, polymorphous low grade adenocarcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas. RESULTS: Tumor cells of monomorphic adenomas were negative for both HA and CD44, and tumor capsules were intensely HA-positive. Pleomorphic adenomas exhibited HA and CD44 positivity in both mesenchymal and epithelial components, and HA in capsular tissues. All malignant salivary gland tumors expressed similar intense HA in tumor stroma. HA staining was more intense in stroma than in parenchymal cells. Tumor cells of most adenoid cystic carcinomas were HA-positive, while most polymorphous low grade adenocarcinomas were HA-negative. HA was uniformly distributed throughout supporting stroma of high and low grade malignancies, except for two polymorphous low grade adenocarcinomas (PLGAs) in which HA was more intense at the invading edge of the tumors. CD44 expression was seen only in tumor cells (not stroma) of malignancies, and was of similar intensity in both low and high grade tumors. CONCLUSIONS: Differences in the expression of HA and CD44 among different types of salivary gland tumors were noted. These findings, however, could not be correlated with known biologic behaviors of the tumor groups studied. Immunohistochemical staining of salivary gland tumors for HA and CD44 may be useful in separating monomorphic adenoma, polymorphous low grade adenocarcinoma and adenoid cystic carcinoma, lesions that may be difficult to distinguish with routine light microscopy.     

Significant correlation between matrix metalloproteinase activity and tumor necrosis factor-oc in salivary extravasation mucoceles

Hoque MO, Azuma M, Sato M: Significant correlation between matrix metalloproteinase activity and tumor necrosis factor-a in salivary extravasation mucoceles. J Oral Pathol Med 1998; 27: 30–3. © Munksgaard, 1998.
We examined the matrix metalloproteinase (MMP) activity and tumor necrosis factor (TNF)-a in luminal fluid of 18 extravasation mucoceles and in saliva from Wharton's duct of five patients by means of gelatin zymography and enzyme immunoassay, respectively. The luminal fluid showed a high level of MMP activity compared with the saliva. Quantitative determination by enzyme immunoassay revealed that the luminal fluid contained higher levels of TNF-a than the saliva. In addition, the amount of TNF-a in luminal fluid exhibited a direct correlation with MMP activity estimated by densitometric analysis of gelatin zymograms. Since TNF-a stimulates the production of MMPs from cells such as fibroblasts, these results suggest that TNF-a is one of the causal molecules that enhance the accumulation of proteolytic enzymes in luminal fluid of mucoceles.     

涎腺肿瘤核仁形成区大小和数目的相关关系

采用银染核仁形成区技术，研究了７６例涎腺肿瘤的核仁形成区（ＮＯＲ），用图象分析系统观察ＡｇＮＯＲ的形态，计算其数量和测量其直径及面积。结果表明，ＡｇＮＯＲ计算值、面积和直径基本上与肿瘤的生物学行为平行，其差异在三组肿瘤间有统计学意义（Ｐ〈０．０１）。ＡｇＮＯＲ计算值与其直径或面积间存在负相关关系，而面积与直径间则存在密切的正相关关系。表明结合ＡｇＮＯＲ计数值及其直径或面积，更有助于对涎腺肿瘤作出鉴     

涎腺肿瘤中端粒酶活性的检测及意义

目的 :探讨端粒酶活性在肿瘤诊断中的意义。方法 :采用非放射性同位素端粒酶重复扩增酶标法对2 9例涎腺肿瘤及 5例正常涎腺组织端粒酶活性进行检测 ,同时还对其中 5例涎腺肿瘤的细针穿刺细胞学检查标本进行了端粒酶活性检测。结果 :16例恶性涎腺肿瘤中 13例为端粒酶阳性 ,占本组恶性涎腺肿瘤的81% ,2例高分化粘液表皮样癌和 1例腺样囊性癌示端粒酶阴性。在 13例良性涎腺肿瘤中仅 1例端粒酶弱阳性。 5例正常涎腺组织端粒酶活性皆为阴性。 5例细针穿刺细胞学检查标本端粒酶活性检测显示 :3例恶性涎腺肿瘤中 2例端粒酶阳性 ,1例端粒酶阴性 ;2例良性涎腺肿瘤端粒酶阴性。结论 :把端粒酶作为新的肿瘤基因诊断的标志物是很有可能的     

Evaluation of salivary gland tumors with 99mTc-pertechnetate

The clinical efficacy of salivary gland scintigraphy was evaluated in 32 histologically proven cases. In benign tumors, except Warthin's tumor, 16 of the 20 cases (80%) appeared as cold lesions. All six cases of Warthin's tumor appeared as hot lesions. In malignant tumors, one case each of mucoepidermoid carcinoma, adenopapillary carcinoma, and adenoidcystic carcinoma were shown as cold lesions, while squamous cell carcinoma and malignant mixed tumor were delineated as a defect image (no uptake of radionuclide). On stimulation with ascorbic acid, retention of radionuclide within the tumor was noted only in Warthin's tumors, but it was noted at the periphery of the tumors in 21 of the 24 cases (87.5%), which might be due to inflammation and/or compression of the gland by the tumors. Salivary gland scintigraphy provided useful information for the evaluation of the site of the tumor and the function of the salivary gland.     

Endothelin expression in salivary gland

The present paper reviews the roles of endothelin (ET) in the rat submandibular gland (SMG). ET and its mRNA are expressed in the granular convoluted tubule (GCT) segment by immunostaining and in situ hybridization, respectively. ET is synthesized in granular cells of the GCT segment, stored in secretory granules, and secreted into the oral cavity. It is well known that granular cells in the GCT segment of the SMG in mice and rats express many kinds of growth factor such as epidermal growth factor and nerve growth factor. These growth factors are discharged into saliva and thought to regulate oral-esophageal and gastrointestinal mucosa. ET acts as a potent vasoconstrictor with mitogenic property and is excreted from Weibel-Palade bodies in vascular endothelial cells. ET in the salivary origin may regulate its own functions as noted in the endothelial origin. This review deals with comparative discussion of ET and other growth factors, which originate from GCT segments in rodents.     

Diffusion MRI: literature review in salivary gland tumors

Surgical resection is currently the best treatment for salivary gland tumors. A reliable magnetic resonance imaging mapping, encompassing tumor grade, location, and extension may assist safe and effective tumor resection and provide better information for patients regarding potential risks and morbidity after surgical intervention. However, direct examination of the tumor grade and extension using conventional morphological MRI remains difficult, often requiring contrast media injection and complex algorithms on perfusion imaging to estimate the degree of malignancy. In addition, contrast‐enhanced MRI technique may be problematic due to the recently demonstrated gadolinium accumulation in the dentate nucleus of the cerebellum. Significant developments in magnetic resonance diffusion imaging, involving voxel‐based quantitative analysis through the measurement of the apparent diffusion coefficient, have enhanced our knowledge on the different histopathological salivary tumor grades. Other diffusion imaging‐derived techniques, including high‐order tractography models, have recently demonstrated their usefulness in assessing the facial nerve location in parotid tumor context. All of these imaging techniques do not require contrast media injection. Our review starts by outlining the physical basis of diffusion imaging, before discussing findings from diagnostic studies testing its usefulness in assessing salivary glands tumors with diffusion MRI.     

Prolactin binding in minor salivary gland tumors

An immunohistochemical study of 15 minor salivary gland tumors was initiated to determine if prolactin binding occurred in these tissues. Eight benign mixed tumors (BMT) and 7 adenoid cystic carcinomas (ACC) were selected at random from the surgical biopsy service of the MCV/VCU School of Dentistry, Department of Oral Pathology. The specimens were cut and mounted on slides along with sections of rat pituitary and rat ventral prostate which served as methodologic controls. Experimental specimens were incubated for 24 hours with varying concentrations of highly purified (iodination grade) rat prolactin; controls were incubated with vehicle. Following incubation the specimens were stained according to the Sternberger peroxidase-antiperoxidase method. Results showed dose-dependent staining for prolactin binding sites in 7 of 8 BMTs and 5 of 7 ACCs. The staining was wider in distribution than we observed in normal human minor salivary gland tissue. Binding was confined primarily to cells of duct origin in both types of tumor. In individual cells, staining was observed in diffuse cytoplasmic and perinuclear locations as well as in nuclei and apical regions. We conclude that two minor salivary gland neoplasms (BMT and ACC) exhibit prolactin binding at different cellular locations and in a more widespread pattern than was observed in normal minor salivary gland.     

Intraoral salivary gland tumors: a retrospective study of 201 cases

Two hundred and one cases of intraoral salivary gland tumors were studied from the files of the School of Pathology, University of the Witwaterstrand and South African Institute for Medical Research. 145 cases (72.5%) were classified as benign, comprising 140 pleomorphic adenomas and 5 monomorphic adenomas. The other 56 cases were classified as malignant or potentially malignant tumors, represented by 21 adenoid cystic carcinomas, 15 adenocarcinomas, 13 mucoepidermoid tumors, 5 carcinoma in pleomorphic adenomas and 2 epidermoid carcinomas. The patients in the malignant/potentially malignant group were significantly older than those in the benign group and a smaller proportion of their tumors were palatal, the difference being statistically significant. The high frequency of pleomorphic adenoma might result from a relatively higher number of black than white patients in this sample.