涎腺粘液表皮样癌中Caveolin-1、PCNA的表达及意义

目的：研究Caveolin-1、增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）在涎腺粘液表皮样癌中的表达,分析二者的关系及其与肿瘤生物学行为间的关系。方法：采用SP免疫组化技术检测75例涎腺粘液表皮样癌标本及20例正常涎腺组织中Caveolin-1、PCNA的表达,并行统计学分析。结果：Caveolin-1在20例正常涎腺组织中均呈阳性表达。Caveolin--1表达下调与病程短、病理级别及临床分期的增高有关,短病程组和长病程组间（42．1％VS67．6％）、低分化和高分化组问（38．5％VS63．3％）、Ⅲ＋IV期和I＋Ⅱ期组间（33．3％VS64．7％）比较差异有统计学意义（P〈O．05）。PCNA随着病理级别和临床分期的增高阳性表达率升高,低分化和高分化组间（33．38土11．98VS20．12士10．13）、HI＋IV期和I＋Ⅱ期组间（29．45土12．89VS22．49士11．73）比较差异有统计学意义（P〈O．05）。Caveolin--1与PCNA的表达呈负相关（rs－0．28,P－0．017）。Caveolin--1表达降低及PCNA表达增高与肿瘤复发显著相关（P〈O．05）。结论：Caveolin-1的表达对粘液表皮样癌细胞增殖起抑制作用,Caveolin--1是影响粘液表皮样癌发生发展的重要因素之一。     

Survivin 和 PDCD5在黏液表皮样癌组织中的表达及临床意义

目的：探讨存活素（Survivin）和细胞程序性死亡因子5（PDCD5）在黏液表皮样癌组织中的表达及临床意义。方法：采用免疫组化 Elivision 二步法检测20例正常腮腺组织（A 组）、40例多形性腺瘤（B 组）及45例黏液表皮样癌（C 组）组织中 Survivin 和 PDCD5蛋白的表达情况。结果：（1）Survivin 在 A、B、C 组中表达阳性率分别为10％、27．5％、55．6％（χ2＝14．556,P ＜0．01）,PDCD 表达阳性率分别为85％、65％、33．3％（χ2＝17．439,P ＜0．01）;（2）Survivin 和 PDCD5的表达与肿瘤的分化程度、有无淋巴结转移及 TNM分期有关（P ＜0．05）;（3）Survivin 和 PDCD5在黏液表皮样癌中的表达呈负相关（χ2＝4．500,P ＝0．034,γs ＝－0．316）。结论：Survivin 高表达,PDCD5低表达在在黏液表皮样癌发生发展中可能发挥作用。     

OPN及β-catenin在涎腺黏液表皮样癌中的表达及意义

目的：研究OPN及β-catenin在黏液表皮样癌中的表达，探讨其在黏液表皮样癌病变中的作用及其临床意义。方法：应用免疫组织化学S—P法检测35例黏液表皮样癌及12例正常涎腺组织中β-catenih及OPN的表达。结果：黏液表皮样癌中β-catenin和OPN的阳性表达率分别为37．1％（13／35）和65．7％（23／35）与正常对照组存在显著性差异（P〈0．05）。在黏液表皮样癌中它们的表达呈显著相关性（P=0．0001，R=-0．691）。β-catenin和OPN的阳性率在不同分化程度的黏液表皮样癌中存有差异（P〈0．05），且与是否存在淋巴结转移有显著性关系（P〈0．05）。结论：β-catenin及OPN的表达与黏液表皮样癌的发生和发展关系密切，检测该指标有助于判断黏液表皮样癌的病理分级和淋巴结转移的关系。     

增殖细胞核抗原和p53蛋白在涎腺肿瘤中的表达

为了研究增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）和ｐ５３在涎腺肿瘤中的表达，作者用抗ＰＣＮＡ及ｐ５３单克隆抗体对良、恶性混合瘤及粘液表皮样癌组织标本进行了免疫组化染色。结果表明，恶性混合瘤ＰＣＮＡ增殖指数较高，与混合瘤细胞生长活跃型及混合瘤相比差异有极显著性（Ｐ＜０．０１）；低分化粘液表皮样癌的ＰＣＮＡ阳性表达明显高于高分化型（Ｐ＜０．０１）。ｐ５３在恶性混合瘤中阳性表达率高（６０．０％），与粘液表皮样癌（２０．０％）相比差异有显著性（Ｐ＜０．０５）。另外，我们观察到ｐ５３阳性表达的肿瘤组织ＰＣＮＡ增殖指数较高。结论：ＰＣＮＡ增殖指数可以作为支持诊断恶性混合瘤的指标；是粘液表皮样癌组织学分级的重要参数。ｐ５３蛋白是恶性混合瘤的有效标记物；ｐ５３蛋白参与ＰＣＮＡ表达的调节。     

EGFR、PCNA、LN、IV型胶原在SACC中的表达及临床意义

目的：探讨表皮生长因子受体（EGFR）、增殖细胞核抗原（PCNA）、层黏连蛋白（LN）和IV型胶原蛋白在唾液腺腺样囊性癌（SACC）中的表达及临床意义。方法：选取临床病例资料齐全的SACC 78例,用荧光原位杂交技术检测EGFR基因表达,免疫组织化学技术检测 EGFR、PCNA、LN和Ⅳ型胶原蛋白的表达,分析其与临床病理参数的相关性。结果：SACC中EG-FR基因扩增率（69．2％）与蛋白的阳性表达率（71．8％）存在明显正相关（P＜0．05）,且EGFR、PCNA、LN、Ⅳ型胶原蛋白表达与临床病理参数密切相关。EGFR、PCNA表达水平间存在明显正相关（P＜0．05）;LN蛋白、Ⅳ型胶原表达水平间存在明显负相关（P＜0．05）。结论：EGFR基因在SACC中明显扩增,EGFR、PCNA、LN、Ⅳ型胶原蛋白共同参与SACC发生、发展。     

HER-2/neu及β-catenin在涎腺粘液表皮样癌中的表达及意义

目的：研究HER-2/neu及β-catenin在粘液表皮样癌中的表达,探讨其在粘液表皮样癌中的作用及其临床意义。方法：应用免疫组织化学S-P法检测42例粘液表皮样癌及10例正常涎腺组织中HER-2/neu及β-catenin的表达。结果：粘液表皮样癌中HER-2/neu和β-catenin的阳性表达率分别为69.05%（29/42）和35.71%（15/42）与正常对照组存在显著性差异（P＆lt;0.05）。HER-2/neu和β-catenin的阳性率在不同分化程度的粘液表皮样癌中存有差异（P＆lt;0.05）,β-catenin的表达与是否存在淋巴结转移有显著性关系（P＆lt;0.05）。结论：HER-2/neu及β-catenin的表达与粘液表皮样癌的病理分级有显著相关性,β-catenin与肿瘤转移明显相关,它们可作为判断肿瘤预后的辅助指标。     

涎腺腺样囊性癌中p53、PCNA评分和Bcl-2表达与病理分型和复发的关系

目的 :探讨涎腺腺样囊性癌中 p5 3 ,增殖细胞核抗原 (PCNA) ,Bcl -2表达与病理分型及复发的关系。方法 :免疫组化SP法对 5例正常涎腺组织和 47例癌组织中p5 3蛋白、PCNA、Bcl-2表达进行检测。结果 :癌组织中 p5 3阳性表达 2 3例 ( 4 8.94% ) ,PCNA评分均数为 2 .40 0± 0 .870 ,Bcl-2蛋白阳性表达 2 3例 ( 4 8.94% )。癌组织中筛孔型和腺管型中 p5 3阳性率和PCNA评分均低于实性型 (P <0 .0 5 )。Bcl-2在筛孔型和腺管型中阳性表达率高于实性型 (P <0 .0 5 )。复发组p5 3阳性表达率和PCNA评分均高于无复发组 (P <0 .0 5 ) ,Bcl -2阳性表达率间差异无统计学意义 (P >0 .0 5 )。结论 :p5 3 ,PCNA ,Bcl-2表达与腺样囊性癌组织分化程度和恶性程度有关。p5 3 ,PCNA评分可以作为预测腺样囊性癌复发的独立指标。     

增殖细胞核抗原和Ki-67抗原在黏液表皮样癌中的表达

目的:检测细胞增殖核抗原(PCNA)和Ki-67抗原在黏液表皮样癌中的表达,探讨其表达量与粘液表皮样癌分级的相关性及意义。方法:对17例黏液表皮样癌的临床病理特点进行回顾性分析,采用SABC和LSAB免疫组化法分别检测PCNA和Ki-67在17例黏液表皮样癌的表达和分布。结果:17例黏液表皮样癌中,高分化型11例(其中1例转移)。低分化型6例(其中4例转移)。PCNA及Ki-67的增殖指数(PI值)在黏液表皮样癌中,低分化型明显高于高分化型(P<0.001)。在发生转移的黏液表皮样癌组中,PCNA及Ki-67的表达水平均明显高于无转移组。结论:黏液表皮样癌中PCNA和Ki-67的表达水平与细胞分化有关,其PI值可作为组织学分级的重要参数。PCNA和Ki-67的高表达预示着黏液表皮样癌预后的不良。     

口腔鳞癌中hTRT mRNA的表达及其与PCNA关系的探讨

目的：探讨端粒酶逆转录酶（hTRT)在口腔鳞癌、癌旁组织的表达及其与增殖细胞核抗原（PCNA）之间的关系。方法：用原位杂交技术及免疫组化方法检测52例口腔鳞癌标本。结果：正常癌旁上皮、上皮异常增生组织及鳞癌hTRT mRNA阳性率分别为20％、41．7％、82．7％。PCNA阳性组与阴性组间hTRT表达水平有显著差异（P＜0．05）。结论：hTRT在口腔鳞癌发生、发展中起重要作用，hTRT与PCNA阳性表达呈正相关，表明hTRT激活细胞多处于高增殖状态。     

涎腺粘液表皮样癌中P53基因表达的研究

目的 探讨Ｐ５３基因在涎腺粘液表皮样癌发生中的作用和意义。方法 采用免疫组织化学方法对４０例涎腺粘液表皮样癌中的表达进行观察。结果 低分化粘液表皮样癌过度表达Ｐ５３基因,阳性表达率为４２．１％,高分化粘液表皮样癌不表达Ｐ５３。经统计学分析表明,高、低分化肿瘤之间差异有显著性。结论 高、低分化的粘液表皮样癌发生时在癌基因激活方面存在差异。Ｐ５３基因突变可能在低分化粘液表皮样癌的发生中具有重要意义。Ｐ     

黏液表皮样癌中CEACAM5和CEACAM6的表达及意义

目的检测癌胚抗原相关细胞黏附分子5(CEACAM5)和癌胚抗原相关细胞黏附分子6(CEACAM6)在涎腺黏液表皮样癌(MEC)组织中的表达情况,分析二者与涎腺黏液表皮样癌发生发展的关系。方法 60例黏液表皮样癌标本,以30例癌旁正常涎腺组织作对照,通过免疫组化法分别检测CEACAM5和CEACAM6在标本中的表达情况。结果 MEC组中CEACAM5和CEACAM6的蛋白阳性表达率分别为(68.3%,65%),明显高于正常涎腺组织中的表达率(40%,36.7%)(P<0.05),MEC组中CEACAM5和CEACAM6蛋白的阳性表达与MEC的分化程度、临床分期及颈部淋巴结转移密切相关(P<0.05),与患者的性别和年龄无关(P>0.05)。CEACAM5和CEACAM6在MEC组织中的阳性表达呈正相关。结论 CEACAM5和CEACAM6在黏液表皮样癌组织中的异常表达促进肿瘤的发生,均参与肿瘤的进展,联合检测可能与患者的预后密切相关。     

核因子κB/B细胞淋巴瘤2信号通路与糖原合成激酶3β在口腔鳞状细胞癌中的表达及临床意义

目的 初步探讨核因子κB（NF-κB）/B细胞淋巴瘤2（Bcl-2）信号通路与糖原合成激酶3β（GSK-3β）在口腔鳞状细胞癌（OSCC）组织中的表达情况,为OSCC的早期诊断及治疗提供参考。方法 收集OSCC标本55例及癌旁组织10例,采用免疫组织化学SP法检测OSCC组织及癌旁组织中GSK-3β、NF-κB及Bcl-2的表达情况,并分析三者相互之间的表达关系及三者与患者临床病理参数之间的关系。结果 GSK-3β、NF-κB及Bcl-2在OSCC中的表达高于癌旁组织中的表达（P<0.01）,且三者与患者年龄、性别以及临床分期无明显关系（P>0.05）。Bcl-2在不同组织学分化程度的OSCC组织中的表达有统计学差异（P<0.05）,而GSK-3β及NF-κB在不同组织学分化程度的OSCC中的表达无统计学差异（P>0.05）。GSK-3β、NF-κB及Bcl-2在OSCC中的表达均两两相关（P<0.05）。结论 GSK-3β、NF-κB及Bcl-2在OSCC组织中的表达显著高于癌旁组织中的表达,检测GSK-3β、NF-κB及Bcl-2的表达水平对于OSCC的早期诊断和预后估计有一定的临床意义。     

Prognostic factors in mucoepidermoid carcinomas of major salivary glands: A clinicopathologic and flow cytometric study

Mucoepidermoid carcinomas (MEC) of the major salivary glands from 48 patients who received their treatment at a single institution were studied for prognostic indicators. Uni- and multivariate statistical analyses were performed on several clinicopathologic factors and also on flow cytometric (FCM) DNA content data of the carcinomas. Clinical prognostic factors associated with decreased survival included age > 60 years (P=0.01), male gender (P=0.002), symptoms at diagnosis (P=0.03), stage of disease (P⩽0.0001), type of surgery (P=0.0006), and recurrence (P=0.0001). Histopathological prognostic factors associated with decreased survival included MEC tumour grade (P=0.0001), tumour size > 3.0 cm (P=0.02), lymph node involvement (P=0.0004) and positive surgical margins (P=0.007). DNA FCM factors associated with decreased survival included aneuploid tumours (P=0.08) and proliferative activity (S + G₂M > 5%, P=0.07). Multivariate analysis indicated that histological grade, proliferative activity, symptoms at diagnosis, clinical stage of disease and type of surgery were significant (P⩽0.05) prognostic/survival factors in the biological assessment of this neoplasm.     

Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours

Background:  Recent studies have proposed that minichromosome maintenance (Mcm) proteins may be sensitive proliferation markers and may serve as novel biomarkers for prognostication and diagnosis of various pre-malignant and malignant lesions. The aims of this study were to determine the expression of Mcm-2, Ki-67 and geminin in salivary gland (SG) tumours, and to evaluate their usefulness for diagnosis or for prediction of tumour behaviour.
Methods:  Tissue from 62 SG tumours was assembled in tissue microarray format. There were 13 adenoid cystic carcinomas (ACC), 10 carcinoma ex pleomorphic adenomas (CEPA), 10 mucoepidermoid carcinomas (MEC), 10 polymorphous low-grade adenocarcinomas (PLGA), 10 pleomorphic adenomas (PA) and nine acinic cell carcinomas (AcCC). Clinicopathological data were collected retrospectively and immunohistochemical analyses of Mcm-2, Ki-67 and geminin were performed on all lesions. Labelling index (LI) for each marker was determined by counting the percentage of positive cells in six random fields from three arrays per case.
Results:  Mcm-2 expression was higher than Ki-67 and geminin in all tumours studied. Mcm-2 LI was higher in ACC (28.2 ± 19.2%) than in CEPA, AcCC, MEC, PA and PLGA (5.3 ± 4.1%, P  = 0.001). Mcm-2 LI was higher in CEPA (20.4 ± 5.0%) than in PA (6.9 ± 5.0%, P  = 0.001). LI did not correlate to tumour grade or outcome for any of the markers or tumour types.
Conclusions:  The findings suggest that Mcm-2 may be a sensitive proliferation marker in SG tumours and may be useful for differential diagnosis between PA and CEPA, and ACC and PLGA. Further studies are warranted to assess the value of Mcm-2 as a predictor of recurrence and survival.     

Prognostic factors in primary salivary gland mucoepidermoid carcinoma: an analysis of 376 cases in an Eastern Chinese population

Mucoepidermoid carcinoma (MEC) is an infrequent malignant neoplasm that originates most commonly in the salivary glands. The present study aimed to provide new information on prognostic factors in patients with salivary gland MEC. A retrospective analysis of the medical records of patients diagnosed with primary salivary gland MEC between 2003 and 2010 was conducted. The incidence of MEC in the minor salivary glands (62.2%) was almost twice that in the major salivary glands (37.8%). The most frequently affected sites were the parotid gland and palate. Lymph node metastasis was reported more frequently in male than female patients (P = 0.02), in high-grade than low/intermediate grade lesions (P < 0.001), and in lesions involving the submandibular gland (P < 0.001). The disease-free survival (DFS) at 5 years was 80.47%, with rates of 98.0%, 86.5%, and 38.5% for low-, intermediate-, and high-grade tumours, respectively. Among various clinicopathological factors, the only independent prognostic factor was histological grade (P < 0.001). Primary tumour site and histological grade are two important factors affecting cervical lymph node metastasis. Histological grade is the only independent factor affecting survival beyond tumor lymph node metastasis (TNM) staging in salivary gland MEC. Further advances in therapy are needed to improve the outcomes for patients with high-grade lesions.     

Increased expression of MUC1 predicts poor survival in salivary gland mucoepidermoid carcinoma

BackgroundMucoepidermoid carcinoma (MEC) is a malignant neoplasm that originates most commonly in the major and minor salivary glands. The aim of this study is to determine the relationship between mucin-1 (MUC1) expression and patient outcome based on a large number of cases.Patients and methodsSurgical specimens from 357 patients with primary salivary gland MEC and 10 patients with normal salivary gland tissue were examined by immunohistochemistry. The relationship between MUC1 expression and the clinicopathological data and patient survival was analyzed.ResultsResults showed that MUC1 expression level was higher in MEC tissues than in paired normal tissues (P = 0.001), and the expression level of MUC1 was significantly associated with gender (P = 0.02), location (P = 0.001), grade (P = 0.001), stage (P = 0.0018) and lymph node metastasis (P = 0.001). In addition, increased expression of MUC1 was confirmed as a strong predictor of poor survival in salivary gland MEC (HR 2.175 [95% CI 1.263, 3.745]; P = 0.0051).ConclusionThe findings indicate that an increased expression of MUC1 may be of great value in assessing the development and prognosis of salivary gland MEC, and could be used as a new molecule target to improve outcomes for these patients in the future.     

凋亡蛋白Bcl-2、Bax在白斑、口腔扁平苔藓中的表达

目的:观察凋亡蛋白Bcl-2、Bax在白斑、口腔扁平苔藓上皮细胞中的表达,探讨其在口腔白斑、口腔扁平苔藓癌变过程中的作用机制。方法:采用免疫组化法检测10例正常口腔黏膜上皮、18例口腔扁平苔藓、23例白斑、22例口腔鳞癌上皮组织中凋亡相关蛋白Bcl-2、Bax的表达水平。结果:Bcl-2在白斑、口腔扁平苔藓上皮细胞层无异常表达,但在口腔扁平苔藓淋巴细胞浸润带过度表达。Bcl-2在鳞癌组织中呈高表达,与正常黏膜相比有显著性差异(P<0.05)。Bax在上皮单纯增生、轻度、中度不典型增生和低分化鳞癌及糜烂型口腔扁平苔藓组织中呈过度表达,与正常黏膜相比有显著性差异(P<0.05)。结论:Bax参与了口腔白斑癌变的早期事件,而Bcl-2在不典型增生转化为鳞癌的阶段并未发生作用。口腔扁平苔藓的发病机制可能与Bcl-2抑制淋巴细胞凋亡,使细胞免疫亢进,从而刺激上皮细胞Bax过度表达,诱导角朊细胞凋亡有关。