Expression of E-cadherin, CD44s, and CD44v6 in laryngeal and pharyngeal carcinomas

OBJECTIVE: Tumors arising from different sites of the head and neck area have very different clinical behavior. Loss or reduction of expression of adhesion molecules has been assumed to play a critical role in the development of head and neck carcinomas. The aim of this study is to determine if there are differences in the expression of adhesion molecules E-cadherin, CD44s, and CD44v6 in pharyngeal and laryngeal squamous-cell carcinomas. MATERIALS AND METHODS: E-cadherin, CD44s, and CD44v6 expression was determined by immunohistochemistry in paraffin-embedded tissue specimens from 72 patients with squamous-cell carcinoma, 37 of the pharynx and 35 of the larynx. RESULTS: Expression of CD44s was significantly lower in pharyngeal than in laryngeal tumors (P =.01). No differences in the expression of E-cadherin and CD44v6 were observed between these sites. CONCLUSIONS: These data suggest that there are some differences at molecular level between the different subsites of head and neck cancer.     

c-myc癌基因蛋白在喉癌及癌旁不同距离组织中的表达研究

应用枸橼酸－ＬＳＡＢ－微波免疫组化法，检测ｃ－ｍｙｃ癌基因蛋白在喉癌、边缘区及癌旁０．５、１．０、１．５、２．０ｃｍ处粘膜和４例正常喉粘膜中的表达。结果：ｃ－ｍｙｃ蛋白在喉癌组织中的阳性表达率为９６．７％（２９／３０），与正常组织相比有极显著性差异（Ｐ〈０．０１）；在癌旁２．０ｃｍ处与１．５ｃｍ以内组织的表达存在着显著性差异（Ｐ〈０．０５）。ｃ－ｍｙｃ表达依正常粘膜→癌旁组织→癌呈逐步递增趋势。ｃ     

Study on ceramide expression and DNA content in patients with healthy mucosa, leukoplakia, and carcinoma of the larynx

OBJECTIVE: To investigate the expression of ceramide produced by sphingomyelin and DNA content in patients with healthy laryngeal mucosa, leukoplakia, and laryngeal carcinoma. DESIGN: A retrospective review of the clinical and surgical records of 178 patients with leukoplakia of the larynx; 23 of them developed laryngeal carcinoma. SETTING: University medical center. PATIENTS: One hundred seventy-eight consecutive patients with leukoplakia of the larynx were identified from the archived pathology files of the Eye Ear Nose and Throat Hospital of Fudan University from January 1, 1990, to December 30, 2001. Among them, 23 developed laryngeal carcinoma. Flow cytometry and immunohistochemistry were performed to test DNA content and ceramide expression in healthy tissue, tissue with leukoplakia, and tissue with laryngeal carcinoma from the same patient. RESULTS: Among 23 patients with leukoplakia, 20 had aneuploidy and 3 had diploidy. The healthy tissues were all diploids, and the tissues with laryngeal carcinoma were all aneuploids. The expression of ceramide decreased gradually from healthy tissue to tissue with leukoplakia to tissue with laryngeal carcinoma (0, no staining; 1+, weak staining; 2+, mild staining; 3+, moderate staining; 4+, strong staining; and 5+, the highest staining intensity). The expression of ceramide in DNA diploid cells is stronger than in aneuploid cells. CONCLUSIONS: Ceramide, the second messenger in apoptosis, may associate with the progress of leukoplakia to carcinoma of the larynx. The reduction of ceramide may contribute to laryngeal carcinogenesis.     

咽喉鳞癌组织中增殖细胞核抗原和核仁组成区相关嗜银蛋白的表达

目的 :研究 4 3例喉癌和 18例下咽癌术后标本中增殖细胞核抗原 (PCNA)的表达并对核仁组成区相关嗜银蛋白 (AgNOR)计数 ,分析其与临床分期、病理分化、复发、转移、生存期之间的相关性 ,评估其对预后及监测患者病情的价值。方法 :采用免疫组化法及Crocker’sAgNOR染色技术定量观察 6 1例鳞状细胞癌术后标本及9例良性喉肿瘤患者的非瘤区粘膜中PCNA的表达及AgNOR计数。分析其与喉癌及下咽癌临床分期、病理分级、复发、转移、生存期之间的相关性。结果 :PCNA阳性细胞百分率 (PCNA指数 )与AgNOR计数呈正相关 ;PC NA指数与AgNOR计数由早期到晚期 ,由高分化到低分化逐渐提高 ;两者在复发、转移及期内死亡患者的癌组织中增加 (P <0 .0 5 )。结论 :PCNA指数和AgNOR计数可作为喉及下咽鳞癌的诊断性预测指标。     

Soluble Adhesion Molecules and Cytokines in Tumor-associated Tissue Eosinophilia of Nasopharyngeal Carcinoma

The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils breaking through the vascular wall and pervading the tumor stroma. The margination and trans-endothelial migration of eosinophils in a typical inflammatory reaction depend on the activating effects of certain cytokines and the expression of adhesion molecules on the eosinophils and endothelial cells. In order to investigate whether the adhesion molecules and activating cytokines play a role in eosinophil tumor infiltration, we measured the serum levels of 3 adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and 40 normal healthy subjects. We found that the NPC patients had higher serum levels of all three soluble adhesion molecules than the normal subjects but the levels of adhesion molecules failed to correlate with the TATE phenomenon. The levels of IL-3 and IL-5 appeared not to differ between the NPC and control groups. We postulate that the three soluble adhesion molecules do not play a major role in TATE and that their elevation in serum may be due to local and/or systemic immune responses.     

Soluble adhesion molecules and cytokines in tumor-associated tissue eosinophilia of nasopharyngeal carcinoma

The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils breaking through the vascular wall and pervading the tumor stroma. The margination and trans-endothelial migration of eosinophils in a typical inflammatory reaction depend on the activating effects of certain cytokines and the expression of adhesion molecules on the eosinophils and endothelial cells. In order to investigate whether the adhesion molecules and activating cytokines play a role in eosinophil tumor infiltration, we measured the serum levels of 3 adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and 40 normal healthy subjects. We found that the NPC patients had higher serum levels of all three soluble adhesion molecules than the normal subjects but the levels of adhesion molecules failed to correlate with the TATE phenomenon. The levels of IL-3 and IL-5 appeared not to differ between the NPC and control groups. We postulate that the three soluble adhesion molecules do not play a major role in TATE and that their elevation in serum may be due to local and/or systemic immune responses.     

FAK及MMP9在喉鳞状细胞癌中的表达及意义

目的 检测黏着斑激酶(FAK)及基质金属蛋白酶9（MMP9）在喉癌中的表达及意义。方法 采用免疫组化SP法,检测57例喉癌及10例癌旁非癌组织中FAK及MMP9的表达。结果 喉癌组织中FAK及MMP9的阳性表达率分别为66.7％及63.2%,在癌旁非癌组织中表达率分别为10.0%及20.0%,差异有统计学意义（P＜0.05）。二者均与肿瘤的临床分期及淋巴结转移有关（P＜0.05）,与患者年龄、肿瘤大小及分化程度无明显相关,且FAK与MMP9的表达呈显著正相关（P＜0.01）。结论 FAK及MMP9在喉癌中均有高表达,且呈显著正相关,提示二者在喉癌的侵袭转移中可能起相互促进作用。     

Expression of focal adhesion kinase and phosphorylated focal adhesion kinase in squamous cell carcinoma of the larynx

OBJECTIVES: Focal adhesion kinase (FAK) is overexpressed in a variety of human cancers including those derived from the oral cavity. The purpose of this work is to determine the expression patterns of FAK and its activated form, FAK pY397, in squamous cell carcinoma of the larynx and to correlate FAK expression with tumor differentiation and clinical parameters. STUDY DESIGN: A retrospective study using archival tissue. METHODS: Thirty-five paraffin embedded tissue specimens of laryngeal carcinoma were obtained from the Department of Pathology at the University of Florida College of Medicine. Immunohistochemical staining of the specimens for FAK and activated phospho-FAK (FAK pY397) was performed. Intensity of staining, distribution of staining, and percentage of cells stained was determined by one pathologist. RESULTS: There was a statistically significant correlation between FAK staining intensity and tumor differentiation. Poorly differentiated tumors stained more intensely than moderately differentiated tumors (P <.001). There was no correlation between FAK pY397 staining and differentiation (P =.163). However, FAK pY397 staining was unexpectedly found in the nuclei of many specimens. FAK was present in the basal layer of cells within nontransformed squamous mucosa derived from tonsillectomy specimens and in blood vessels. A small amount of FAK pY397 was also localized to blood vessels in nontransformed squamous mucosa. CONCLUSION: FAK and phospho-FAK are overexpressed in squamous cell carcinoma of the larynx. FAK expression correlates with differentiation. Future investigations will examine the potential of FAK and FAK pY397 expression both as a prognostic indicator and a point of therapeutic inhibition.     

雄激素受体mRNA基因在喉癌组织中的表达与研究

以探讨雄激素受体（ＡＲ） ｍＲＮＡ基因在喉鳞状细胞发展中的作用，应用Ｎｏｒｔｈｅｒｎ杂交技术，以及喉癌组织的总ＲＮＡ分离、激光扫描等方法，观察、分析检测了ＡＲ基因在喉鳞状细胞组织中，以及癌旁正常组织中表达及意义。结果显示，２７例喉癌组织中及６例癌旁正常组织中均存在ＡＲ，且喉癌组织中ＡＲｍＲＮＡ基因的表达水平明显高于癌旁正常组织，通常情况下在癌旁正常组织中ＡＲｍＲＮＡ基因的表达水平明显高于癌旁正常组     

转化生长因子β1在喉鳞状细胞癌组织中的表达及其临床意义

目的：探讨转化生长因子β1(TGF—β1)与喉鳞状细胞癌患者的病理分级、临床分期问的相互关系，研究TGF-β1在喉鳞状细胞癌发病机制中的作用。方法：分别提取21例喉鳞状细胞癌组织,15例喉正常组织的总RNA，采用逆转录聚合酶链反应技术，检测TGF-β1 mRNA的水平。结果：21例喉鳞状细胞癌组织中10例(47．62％)TGF-β1 mRNA表达阳性。TGF-β1 mRNA与喉鳞状细胞癌病理分级和临床分期有一定关系。结论：TGF-β1可作为评定喉鳞状细胞癌的进展、浸润的指标。     

Hemipharyngectomy and hemilaryngectomy for pyriform sinus cancer: Reconstruction with remaining larynx and hypopharynx and with tracheostomy

When resection of the posterior hypopharyngeal wall is undertaken for treatment of pyriform sinus carcinoma, a very narrow mucosal strip may be left for reconstruction. A surgical technique for carcinoma which has invaded the whole lateral hypopharyngeal wall is described. It consists of resecting half the larynx and half the hypopharynx and reconstructing the food canal using the mucosa of the unaffected half of the larynx and the remnant hypopharynx. A series of 34 patients treated by this technique is presented. No hypopharyngeal stenosis was observed. Local recurrences developed in 9 cases and distant metastases in 6. A specific disease mortality rate of 44% was encountered. At present, 15 patients are disease-free after a median follow-up of 48 months.     

喉鳞癌组织两种P糖蛋白单克隆抗体的检测

为了解喉鳞癌的多药耐药性，以期提高综合治疗中化疗的效果，采用免疫组化技术对未经任何治疗的喉鳞癌患者在手术中取出的新鲜肿瘤组织进行了Ｐ糖蛋白（ＰＧＰ）单克隆抗体ＪＳＢ１及其单克期抗体Ｃ２１９的检测。对比了肿瘤组织分化程度、肿瘤大小及有无淋巴结转移与ＰＧＰ表达阳性之间的关系。结果发现，单抗ＰＧＰ ＪＳＢ１的阳性率为６５．２％（ｎ＝２３），而单抗Ｃ２１９检测的６例ＰＧＰ均为阴性，与分化无关，与肿瘤大小、     

细胞周期蛋白E和肿瘤转移抑制基因nm23-H1与鼻咽癌

目的 探讨细胞周期蛋白E(cyclin E)和肿瘤转移抑制基因nm23-H1在鼻咽癌组织中的表达及其临床意义.方法 用免疫组化SP法检测42例鼻咽癌和28例正常鼻黏膜上皮的病理组织切片标本中cyclin E和nm23-H1蛋白的表达.结果 cyclin E蛋白在鼻咽癌组织中的阳性表达率为59.5%(25/42),显著高于对照组中的17.9%(5/28);nm23-H1蛋白在鼻咽癌组织中的阳性表达率为42.8%(18/42),显著低于对照组中的100%(28/28);cyclin E蛋白在低分化组和有淋巴结转移组中的阳性表达率分别为74.2%和77.8%,明显高于高、中分化组和无淋巴结转移组中的18.1%和26.7%;nm23-H1蛋白在低分化组和有淋巴结转移组中阳性表达率分别为25.8%和25.9%,明显低于高、中分化组和无淋巴结转移组中的90.9%和73.3%;cyclin E和nm23-H1在鼻咽癌组织中的表达呈负相关.结论 cyclin E过表达和nm23-H1表达下调在鼻咽癌的发生、发展和转移中起重要作用.     

Expression of Adhesion Molecules in Nonallergic Chronic Sinusitis

Endothelial and epithelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. To determine the relationship between recruited leukocytes and adhesion molecules in the paranasal sinus mucosa of nonallergic chronic sinusitis, we surgically obtained mucosa from 16 patients and identified the expression of intercellular adhesion molecules(ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin by immunohistochemistry. Neutrophils were significantly dominant in the nasal discharge as compared with eosinophils. The degree of neutrophil infiltration in the paranasal sinus mucosa was prominent in both intraepithelial and subepithelial areas as compared with the lamina propria. In each tissue site, the degree of infiltration of neutrophils was similar to that of eosinophils. These findings suggest that the tissue neutrophils actively and rapidly migrated into the lumen. All the adhesion molecules except VCAM-1 were expressed in the vascular endothelial cells. On the other hand, the surface epithelial cells showed the expression of only ICAM-1. The expression of ICAM-1 on the endothelial cells correlated with the degree of neutrophil infiltration in the mucosa. The eosinophil infiltration was not dependent on any adhesion molecules examined here. It was concluded that ICAM-1 expression in the mucosa may be involved in neutrophil recruitment and may contribute to the establishment of the inflammatory cell distribution in the paranasal sinus of nonallergic chronic sinusitis.     

Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer

OBJECTIVE: To explore the value of E-cadherin and focal adhesion kinase (FAK) expression in the prediction of cervical lymph node metastases in squamous cell carcinoma of the supraglottic larynx. DESIGN: Immunohistochemical analysis of retrospectively selected cases. Patients The study population was composed of 95 previously untreated men with squamous cell carcinoma of the supraglottic larynx. Intervention All the patients underwent surgical resection of the tumor and bilateral neck dissection. MAIN OUTCOME MEASURES: E-cadherin and FAK expression in relation to nodal metastases. RESULTS: Decreased E-cadherin expression was correlated with the presence of nodal metastases (P = .006). The combination of E-cadherin and FAK expression resulted in a superior accuracy in assessing nodal metastasis (P = .001). Histological grade was also associated with nodal metastases (P = .005). Multivariate analysis confirmed that these parameters were independent predictors of nodal metastases. In addition, the cases with decreased E-cadherin and increased FAK expression presented a significantly reduced disease-specific survival (P = .005). CONCLUSION: The combination of the expression of E-cadherin and FAK could increase our ability to identify patients with clinically negative lymph nodes who are at considerable risk for occult metastases.     

喉癌手术安全切缘的免疫组化研究

目的：从基因蛋白水平角度研究喉癌手术安全切缘。方法：应用 Ｌ Ｓ Ａ Ｂ免疫组化法,检测了ｒａｓ、ｃｍ ｙｃ、ｐ５３ 癌基因在３０ 例喉癌,边缘区,癌旁０．５、１．０、１．５、２．０ ｃｍ 粘膜处和 ４ 例正常喉粘膜中的表达情况。结果：三种癌基因产物的单独及联合表达阳性率依正常粘膜→癌旁２．０ ｃｍ →１．５ ｃｍ →１．０ ｃｍ →０．５ ｃｍ →边缘区→癌顺序递增,且癌基因蛋白的表达在距肿瘤０．５ ｃｍ 以内的癌旁组织与癌旁组织１．０ ｃｍ 处有显著性差异（ Ｐ ＜ ０．０５）。结论：距肿瘤０．５ ｃｍ 内的癌旁组织应视为癌前期病变,以切缘距肿瘤０．５ ｃｍ 作为喉癌手术安全切缘的标准较为合适     

喉癌喉咽癌组织中诱导型一氧化氮合酶的表达及临床意义

目的 :探讨诱导型一氧化氮合酶 (iNOS)在喉癌喉咽癌组织中的表达及其临床意义。方法 :采用逆转录 聚合酶链反应 (RT PCR)技术检测 4 0例喉癌及 12例喉咽癌 (喉癌喉咽癌组 )、5 0例癌旁组织 (癌旁组 )、12例良性肿瘤 (良性肿瘤组 )及 7例正常喉黏膜 (正常喉黏膜组 )组织中iNOSmRNA的表达。结果 :喉癌喉咽癌组阳性表达率为 78.85 % ,与正常喉黏膜组 (0 % )和癌旁组 (2 0 .0 0 % )比较 ,差异有极显著性意义 (P <0 .0 1) ;与良性肿瘤组 (4 1.6 7% )比较 ,差异亦有显著性意义 (P <0 .0 5 )。有局部淋巴结转移组 (95 .2 4 % )显著高于无局部淋巴结转移组 (6 7.74 % ) (P <0 .0 5 ) ;iNOSmRNA阳性表达与T分级呈正相关 (P <0 .0 5 ) ,与细胞分化程度呈负相关 (P <0 .0 5 )。结论 :喉癌喉咽癌组织中iNOSmRNA呈高表达 ,提示iNOS可能通过合成NO在分子水平参与了喉癌喉咽癌的发生、发展 ;NO供体药物和iNOS特异性抑制剂的开发 ,必将为肿瘤治疗带来可喜的前景。     

下咽癌细胞增殖细胞核抗原及其基因的表达研究

目的 :通过对下咽癌细胞增殖细胞核抗原 (PCNA)及其基因的检测 ,以探讨其对下咽癌生物学特性、临床行为及预后的影响。方法 :用免疫组织化学染色SABC法检测 4 8例下咽癌手术标本和同期 1 5例癌旁正常组织标本PCNA的表达 ,计算其增殖指数 ;同时用寡核苷酸探针原位杂交技术检测PCNA的mRNA ,以检验免疫组化与原位杂交结果的一致性。结果 :下咽癌组PCNA增殖指数为 (71 .4 8± 1 1 .1 4 ) % ,对照组为 (2 1 .1 3±1 2 .0 7) % ,其差异有显著性意义 (P <0 .0 5 ) ;PCNA增殖指数与癌的临床分期、组织分化程度及预后相关 ,而与是否有颈淋巴结转移和肿瘤发生部位无明显关系 ,且免疫组化和原位杂交两种检测结果相一致 (符合率为 85 .7% )。结论 :检测下咽癌PCNA的表达可能对判断肿瘤恶性程度及预后有一定的参考价值     

KAI1/CD82在喉癌组织中的表达及其临床意义

目的：探讨KAI1／CD82在喉癌组织中的表达水平及与患者临床病理特征的关系。方法：选取61例喉癌患者手术切除的病理组织标本（喉癌组）及61例癌旁组织标本（对照组），应用免疫组织化学法检测KAI1／CD82的表达水平。结果：喉癌组KAI1／CD82的表达水平低于对照组（P〈0.05）；肿瘤原发灶KAI1／CD82表达水平高于淋巴结转移灶（P〈0.05）；KAI1／CD82的表达水平与喉癌患者的淋巴结转移密切相关（P〈0.05），但在不同年龄、临床分期及组织分化程度的患者之间的表达差异无统计学意义（P〉0.05）。结论：KAI1／CD82的表达在喉癌的转移过程中具有一定作用，可作为预测肿瘤转移潜能的指标。     

发生于耳鼻咽喉部的原发性神经内分泌癌4例

目的：探讨发生于耳鼻咽喉部的原发性神经内分泌癌的的病理、临床特性及治疗方法；方法：喉非典型类癌1例，行会厌切除术；鼻咽部非典型类癌1例。行放疗；中耳类癌1例，行右中耳探查及乳突根治术；右鼻腔小细胞神经内分泌癌1例，行鼻右侧切开肿瘤切除术及放疗。结果：喉非典型类癌及鼻咽部非典型类癌患者分别于5年和1年后死亡；中耳类癌患者随访3年右耳术腔干洁；右鼻腔小细胞神经内分泌癌随访2年未见复发。结论：发生于耳鼻咽喉部的原发性神经内分泌癌可分为类癌、非典型类癌、小细胞神经内分泌癌。类癌为低度恶性。小细胞神经内分泌癌为高度恶性，非典型类癌介于二者之间。治疗以手术切除为主．