CD44蛋白在人喉癌中的表达及其临床意义

目的：ＣＤ４４基因是一各肿瘤转移相关基因。研究检测ＣＤ４４ｖ６蛋白拓喉癌中的表达及其临床意义。方法：用ＣＤ４４ｖ６单克隆抗体,通过免疫组化Ｓ－Ｐ法,对６９例喉鳞状细胞癌蜡块标本和１０例正常喉粘膜标本进行研究,并结合资料进行预后分析。结果：６９例喉鳞状细胞癌、１０例正常喉粘腊中ＣＤ４４ｖ６蛋白阳性表达率分别为５２．２％（３６／３９）和０．０％（０／１０）。ＣＤ４４ｖ６蛋白阳性表达与肿瘤发生部位、病理     

白细胞介素—2局部及全身治疗前后鼻咽癌原发灶CD44v6阳性？…

目的：研究４８例鼻咽癌病人经白细胞介素－２治疗前后ＣＤ４４ｖ６在原发灶中的表达及其临床意义。方法：以免疫组化ＳＰ方法，在鼻咽癌病人经白细胞介素－２治疗前后检测原发灶中ＣＤ４４ｖ６的阳性主强阳性表达率。结果：治疗前ＣＤ４４ｖ６的阳性及强阳性表达率在淋巴结转移组（３４例）「１１．８％，１７．６％」明显低于非转移组（１５例）「４０．０％，２０．０％」；经白细胞介素－２治疗后在局部治疗组（２９例ＣＤ４４Ｖ     

CD44v6在甲状腺乳头状腺癌中的表达及意义

目的：探讨肿瘤转移相关基因ＣＤ４４ｖ６与甲状腺乳头状腺癌颈淋巴结转移及其生物学行为的关系。方法：采用免疫组化ＬＳＡＢ方法对５０例甲状腺乳头状腺癌存档标本进行ＣＤｖ６表达测定。结果：甲状腺乳头状腺癌颈淋巴结转移组２６例ＣＤ４４ｖ６阳性表达率为７６．９％（２０／２６）,颈淋巴结转移阴性组２４例中阳性率为５０．０％（１２／２４）,二者比较Ｐ〈０．０５;ＣＤ４４ｖ６表达阳性率与病人临床Ｔ分期无明显相关性（     

CD44H,CD44V6在下咽癌中的表达及其临床意义

目的：检测下咽鳞癌中粘附分子ＣＤ４４Ｈ,ＣＤ４４Ｖ６的表达情况并分析ＣＤ４４Ｈ,ＣＤ４４Ｖ６的表达与下咽鳞癌临床分级、病理分级、颈淋巴结转移及预后的关系。方法：应用免疫组化ＳＡＢＣ法。结果：ＣＤ４４Ｈ,ＣＤ４４Ｖ６的表达与下咽癌的病理分级呈负相关,即随肿瘤恶性程度的升高,其表达下降。结论：ＣＤ４４Ｈ,ＣＤ４４Ｖ６的表达有助于判断下咽鳞癌恶性程度。     

转移相关基因CD44V6在喉癌中表达及意义

为探讨转移相关基因ＣＤ４４Ｖ６与喉鳞癌颈淋巴结转移和其他生物学行为的关系，采用免疫组化ＳＰ法对３９例喉鳞状细胞癌进行标记分析，结果发现：ＣＤ４４Ｖ６阳性率，淋巴结转移组（８８．２４％）明显高于无淋巴结转移组（５９．０９％），在喉鳞癌Ⅲ级高于鳞癌Ⅰ－Ⅲ级（５０％），对ＣＤ４４Ｖ６阳性的组织切片研究同仁三某些切片中不是全部癌细胞均为ＣＤ４４Ｖ６阳性，有部分癌细胞为阴生反应。上述结果表明，在喉鳞癌组织内     

喉鳞状细胞部Cath—D和CD44的免疫组织化学检测

为研究组织蛋白酶－Ｄ和ＣＤ４４表达与喉癌临床，病理和预后的关系，采用免疫组织化学方法检测Ｃａｔｈ－Ｄ和ＣＤ４４在９６例喉鳞状细胞癌中的表达情况。结果显示，Ｃａｔｈ－Ｄ和ＣＤ４４在喉癌中表达的阳性率分别为５２．１％和４１．７％；Ｃａｔｈ－Ｄ的阳性表达与喉癌转移吴正相关，但单独与颈淋巴结转移无关，ＣＤ４４表达与转移无关；     

CD44蛋白在人喉癌组织中的表达及临床意义

目的：探讨CD44在人喉癌组织中的表达及其临床意义。方法：采用免疫组织化学Envision法对261例喉不同病变组织标本进行CD44表达检测。结果：人喉癌组织中CD44高表达率为70．9％，明显高于癌前病变（16．7％）及正常喉组织（0％），其差异均有极显著性意义（P＜0．01）；喉癌组织中高分化鳞癌CD44表达明显低于低分化鳞癌（P＜0．01）；Ⅲ-Ⅳ期喉癌病变组织CD44表达明显高于I－Ⅱ期（P＜0．01）；有颈淋巴结转移的喉癌组织CD44表达明显高于无颈淋巴结转移的喉癌组织（P＜0．01）；CD44表达阳性病例3、5年生存率明显低于CD44表达阴性病例（均P＜0．05）。结论：喉癌的发生、发展及患者预后与CD44表达密切相关。     

CD44v和nm23—H1基因蛋白在喉癌中的表达及其临床意义

目的 探讨ＣＤ４４ｖ和ｎｍ２３－Ｈ１蛋白在喉癌的表达及其临床意义。方法 采用１９９６年１０月￣１９９８年８月我科住院患者喉鳞癌手术新鲜标本６０例（其中男５２例,女８例,年龄４１￣７７岁）,癌旁组织２０例,喉正常粘膜１２例。采用流式细胞术（ｆｌｏｗ ｃｙｔｏｍｅｔｒｙ,ＦＣＭ）测定了ＣＤ４４ＶＴ ＮＭ２３－Ｈ１蛋白在喉癌的定量表达。结果 ①ＣＤ４４ｖ和ｎｍ２３－Ｈ１蛋白在喉癌组织中的定量表达均高于喉     

喉癌nm23,Cath—D和CD44表达与预后的相关因素分析

目的：探讨影响喉癌预后的相关因素。方法：采用免疫组化检测９６例喉鳞状细胞癌标本表达情况,并结合临床和病理资料分析喉癌预后因素。结果：ｎｍ２３、Ｃａｔｈ－Ｄ和ＣＤ４４的阳性表达率分别为４５．７％（４３／９４）、５２．１％（５０／９６）和４１．７％（４０／９６）。喉癌部位、大小、分化程度、Ｔ分期及ｎｍ２３表达与喉癌颈淋巴结转移有关（Ｐ〈０．０５）。结论：ｎｍ２３在喉癌中表达情况,对预测喉癌颈淋巴结转移     

人血咽癌中CD44V6蛋白产物的表达及临床意义

探讨转移相关基因ＣＤ４４Ｖ６蛋白产物在人鼻咽癌中的表达特点及其与颈淋巴结转移和其它生物学行为的关系。方法采用免疫组化Ｓ－Ｐ法对７３例低分化鼻咽癌和１２例慢性鼻咽炎上皮进行蛋白产物的检测。结论５例慢性鼻咽炎上皮蛋白表达均在基底层。     

p185和CD44v6在喉鳞状细胞癌中的表达及临床意义

目的:探讨癌基因蛋白p185和细胞黏附因子CD44v6在喉鳞状细胞癌(LSCC)中的表达、临床意义及其相关性。方法:采用免疫组织化学SP法检测63例LSCC及其中20例癌旁安全缘组织(ASM)和18例声带息肉(VCP)中p185与CD44v6的表达。结果:p185在VCP中不表达,在LSCC和ASM中的阳性率分别是74.6%、35.0%,两者之间差异有统计学意义;p185在不同病理分级Ⅰ、Ⅱ、Ⅲ级间存在差异(P<0.05);p185在不同临床分期的表达,差异无统计学意义(P>0.05);CD44v6在LSCC、VCP和ASM中的阳性率分别是96.8%、83.3%、60.0%,3者之间差异有统计学意义(P<0.05);CD44v6在不同病理分级Ⅰ、Ⅱ、Ⅲ级及不同临床分期间的表达差异无统计学意义(P>0.05);LSCC中p185与CD44v6的表达存在正相关(r=0.393,P<0.01)。结论:根据实验结果,p185可能在LSCC发生及发展中起重要作用,CD44v6可能只在LSCC的发生中起作用,在癌旁组织中p185与CD44v6的表达均较良性病变中的表达量增加,反映癌旁移行黏膜中两者可能作为不稳定因素与LSCC复发有关,且两者可能存在协同作用。     

CD44v6和MMP-9在喉鳞状细胞癌组织中的表达及意义

目的:研究喉鳞状细胞癌(LSCC)组织中细胞黏附分子CD44变构体6(CD44v6)和基质金属蛋白酶-9(MMP-9)的表达情况及临床意义。方法:应用免疫组织化学SABC法测定27例LSCC组织及8例癌旁正常喉黏膜组织中CD44v6和MMP-9的表达,并分析CD44v6和MMP-9表达与LSCC浸润、转移和预后的关系。结果:CD44v6和MMP-9在LSCC组织中均过度表达。CD44v6表达与LSCC病理分化程度、颈淋巴结转移及术后5年生存率有关(均P<0.05);MMP-9表达与LSCC颈淋巴结转移、临床分期及T分期有关(均P<0.05)。LSCC组织中CD44v6和MMP-9的表达呈显著正相关(均P<0.01)。结论:LSCC组织中CD44v6和MMP-9的表达密切相关。CD44v6和MMP-9的表达可作为临床上判断LSCC浸润、淋巴结转移及评估预后的客观指标。     

Expression of E-cadherin, and CD44s and CD44v6 and its association with prognosis in head and neck cancer

OBJECTIVES: In the current study, the expression of E-cadherin, CD44s, and CD44v6 has been noted as markers for tumor metastasis and prognosis in several tumors, so we examined whether or not E-cadherin, CD44s, and CD44v6 are useful markers for evaluating the prognosis of mesopharyngeal cancer patients. METHODS: The expression of E-cadherin, CD44s, and CD44v6, was evaluated immunohistochemically using monoclonal antibodies against epitopes of standard and variant proteins, in paraffin-embedded mesopharyngeal cancer tissues from 57 patients who had received curative therapy. RESULTS: Tumor tissues from 47 (82.5%) patients showed positive immunoreactivity with monoclonal antibody against E-cadherin, 43 (75.4%) patients showed positive expression with CD44, and 45 (78.9%) patients showed positive expression with CD44v6. The expression of CD44v6 was slightly correlated with tumor volume, and lymph node metastasis, and stage classification (P > 0.05). However, there was no significant correlation between the expression of E-cadherin, CD44s and CD44v6 and clinicopathological characteristics. Concerning the prognosis, the survival period of patients with CD44s positive tumors was shorter than that of patients with CD44s negative tumors (18.2% versus 52.1%, 5-year survival, P > 0.05). The survival period of patients with CD44v6 positive tumors was also shorter than that of patients with CD44v6 negative tumors (12.8% versus 55.6%, 5-year survival, P > 0.05). CONCLUSION: These results suggest that CD44v6 may be related to tumor invasion and metastasis, and both CD44s and CD44v6 may be useful markers for poor prognosis in head and neck cancer.     

Soluble CD44 standard, CD44 variant 5 and CD44 variant 6 and their relation to staging in head and neck cancer

CONCLUSION: The possible roles of CD44st, CD44v5 and CD44v6 in the prognosis of head and neck cancer deserve further elucidation and evaluation with long-term patient follow-up. OBJECTIVE: Standard CD44 (CD44st), CD44 variant 5 (CD44v5) and CD44 variant 6 (CD44v6) are expressed in human malignant cells and tissues. The mechanism of their expression remains unclear, but has been reported to be associated with the progression and metastasis of malignancies. Recently, it has frequently been reported that the prognosis of head and neck cancer is associated with expression of the cell adhesion molecule CD44. MATERIAL AND METHODS: We investigated correlations between the soluble adhesion molecule CD44 and clinicopathologic variables, for example, age, sex, histologic grade, tumor size, lymph node status, distant metastasis and TNM stage. The pre- and post-treatment serum levels of CD44st, CD44v5 and CD44v6 were determined by means of ELISAs in 81 patients with head and neck cancer and 20 healthy volunteers (controls). RESULTS: In the cancer patients, the pre-treatment median serum levels of CD44st, CD44v5 and CD44v6 were 327 +/- 134, 312 +/- 118 and 211 +/ 110 ng/ml, respectively. The corresponding post-treatment levels were 185 +/- 103, 177 +/- 90 and 110 +/- 65 ng/ml. In the healthy volunteers, the median serum levels of CD44st, CD44v5 and CD44v6 were 133 +/- 40, 142 +/- 39 and 86 +/- 22 ng/ml, respectively. In the cancer patients, there was no significant correlation between the serum levels of CD44st, CD44v5 and CD44v6 and the clinicopathological variables. The pre-treatment serum levels of CD44st, CD44v5 and CD44v6 were closely associated with TNM stage (p = 0.0017, 0.0005 and 0.0046, respectively). The median pre-treatment serum levels of CD44st, CD44v5 and CD44v6 were significantly higher than those in the control group (p = 0.0002, 0.0065 and 0.0038, respectively). The median post- treatment serum levels of CD44st, CD44v5 and CD44v6 were significantly lower than the pre-treatment levels (p = 0.0003, 0.0027 and 0.0034, respectively).     

国内CD44v6与喉鳞癌关系研究的Meta分析

目的对CD44v6与喉鳞癌相关性研究的国内文献进行Meta分析,探讨其病理与临床意义。方法检索中国学术期刊全文数据库、维普及万方数据库,收集1996～2006年国内期刊公开发表的有关喉鳞癌CD44v6表达及其意义的独立病例对照研究论文,在对文献进行异质性检验后,以病例组及对照组比值比（OR值）为效应指标,应用Meta分析软件RevMan4．2．9对各研究报告原始数据进行统计处理,计算合并OR值、95％可信区间及Meta分析森林图。结果最终进入系统评价的文献共有7篇,观察癌患者496例,对照病例99例。Meta分析结果,合并区OR为19．43,95％可信间（CI）为[4．14,91．27],CD44v6表达与喉鳞癌临床分期（p〈0．0001）、分化程度（p=0．0004）、淋巴结转移（P〈0．00001）及5年生存率（P=0．002）均存在明显相关性,而与病变分型（P=0．23）及TNM分期（P=0．12）、患者年龄（P=0．53）及性别（P=0．63）无明显关联。结论相关研究文献的Meta分析显示,CD44v6高表达可能在喉鳞癌的发生、发展、转移及预后中起重要作用。     

Evaluation of soluble adhesion molecules CD44 (CD44st, CD44v5, CD44v6), ICAM-1, and VCAM-1 as tumor markers in head and neck cancer

PURPOSE: Standard CD44 (CD44st), CD44 variant 5 (CD44v5), and CD44 variant 6 (CD44v6), intercellular adhesion molecule 1(ICAM-1), and vascular cell adhesion molecule 1(VCAM-1) are expressed in human malignant cells and tissues. Their mechanism remains unclear but has been reported to be associated with the progression and metastasis of malignancies. MATERIALS AND METHODS: In this study, we investigated any correlations between the soluble adhesion molecule CD44 (st, v5, and v6), ICAM-1, and VCAM-1 and the clinicopathologic variables (eg, age, sex, histological grading, tumor size, lymph node status, distant metastasis, and TNM staging) and evaluated the difference between the pretreatment level in the patients with head and neck cancer and that in the control group. Furthermore, we examined the difference between the pretreatment serum levels and the after-treatment serum levels in the group with head and neck cancer. The pretreatment and after-treatment serum levels of soluble CD44st, CD44v5, CD44v6, ICAM-1, and VCAM-1 were measured in 81 patients with head and neck cancer and in 20 healthy volunteers as controls. RESULTS: There were no significant differences between the serum levels of sCD44st, sCD44v5, sCD44v6, sICAM-1, and sVCAM-1 and the clinicopathologic variables in cancer patients. However, the higher serum level of sCD44v6 was significantly associated with distant metastasis (P = .02). Especially, we found that the pretreatment serum levels of sCD44st, sCD44v5, and sCD44v6 were markedly associated with TNM staging (CD44st P = .0017, CD44v5 P = .0005, CD44v6 P = .0046). Furthermore, the median serum levels of sCD44st, sCD44v5, sCD44v6, sICAM-1, and sVCAM-1 before treatment of head and neck cancer were significantly higher than those of the control group (CD44st P = .0067, CD44v5 P = .0048, CD44v6 P = .0007, ICAM-1 P = .0089, VCAM-1 P = .0178). The median serum level of sCD44st after treatment in the group of patients was significantly lower than that of pretreatment (CD44st P = .0001). And, both the median serum levels of sCD44v5 and sCD44v6 after treatment were also lower than those of pretreatment (CD44v5 P = .0004, CD44v6 P = .0025). CONCLUSIONS: The possible roles of soluble adhesion molecules in the prognosis of head and neck carcinoma deserve further elucidation and evaluation with long-term patient follow-up.     

Prognostic value of CD44 variant 6 in laryngeal epidermoid carcinomas

BACKGROUND: CD44 variant exon 6 (v6) belongs to a family of transmembrane glycoproteins involved in cell adhesion. OBJECTIVES: To determine the prognostic role of CD44v6 in laryngeal cancer and to examine its relation with other clinicopathologic prognostic factors. DESIGN: A retrospective cohort study was designed with 93 laryngeal cancer cases. They were selected randomly from patients treated with laryngectomy between January 1, 1983, and December 31, 1993. SETTING: Faculty of Medicine, Hacettepe University, Ankara, Turkey. PATIENTS: The ages of the patients ranged from 31 to 73 years. Eighty-eight patients were men and 5 were women. Three had stage I, 33 had stage II, 27 had stage III, and 30 had stage IV disease at the time of surgery. INTERVENTION: Histological sections of tumors and metastatic lymph nodes were reevaluated for several histopathological factors. Sections were stained using anti-CD44v6 monoclonal antibody by immunohistochemical methods. RESULTS: CD44v6 expression was seen only in the lower one third of the normal squamous epithelium but in all layers of dysplasia and in situ carcinoma. Besides a general evaluation of tumor staining, immunostaining was evaluated separately for cell groups located in the center of neoplastic islands (nonbasal cells), at the periphery of the neoplastic islands (basal cells), and at the infiltration zones (marginal cells). Decreased disease-free survival was noted when there was extensive staining in the general evaluation and in cases with extensive staining in marginal and nonbasal cells (P =.03). Using Cox regression analysis, the greatest dimension of the largest metastatic lymph node and extensive expression of CD44v6 in nonbasal tumor cells were independent prognostic factors. CONCLUSION: Our results suggest that CD44v6 expression is an important prognostic factor in laryngeal cancer.     

Expression of p16, nm23-H1, E-cadherin, and CD44 gene products and their significance in nasopharyngeal carcinoma

OBJECTIVE: The present study was aimed to determine whether p16/MTS1, nm23-H1, E-cadherin, and CD44 proteins were expressed in nasopharyngeal carcinoma (NPC) and whether those expressions were pathologically significant in the progress of NPC. METHOD: We examined non-cancerous nasopharyngeal mucosa (20 cases) and NPC (80 cases) using immunohistochemistry with six different types of monoclonal antibodies against p16, nm23-H1, E-cadherin, CD44H, CD44v3, and CD44v6 proteins. RESULTS: The results showed that 1) the rates of positive p16 protein expression and of preserved E-cadherin protein expression in NPC were significantly lower than those in non-cancerous tissue (P <.01); 2) no significant difference in the rate of positive expression of nm23-H1, CD44H, CD44v3, and CD44v6 proteins were observed between non-cancerous nasopharyngeal mucosa and NPC; 3) no significant difference in the expression of those proteins were found by respective correlation analyses of sex, stage, and size of primary tumor in NPC; and 4) no significant difference in the rates of positive expression of CD44H, CD44v3, and CD44v6 proteins were observed in NPC between with and without lymph node metastasis, indicating that those gene products did not correlate with lymph node metastasis in NPC. However, there were inverse correlations between the expression of p16, nm23-H1, or E-cadherin protein and lymph node metastasis (P <.05), indicating that the expression of p16, nm23-H1, and E-cadherin gene were related to the carcinogenesis and tumor progression of NPC. CONCLUSION: Detecting the expressions of those gene products may provide clinically valuable information for therapeutic strategy and for predicting the prognosis of patients with NPC.     

Role of CD44 variant exon 6 in invasion of head and neck squamous cell carcinoma

OBJECTIVES: To determine the correlation between the expression of CD44 variant exon 6 (v6) and the clinicopathological features of head and neck squamous cell carcinomas (HNSCCs), and to study the role of CD44v6 in cell invasion using a human HNSCC cell line (HSC-2). DESIGN: The expression of CD44v6 was evaluated using immunohistochemical analysis in paraffin-embedded tissue specimens from 89 primary lesions. The concentration of CD44v6 protein in 37 cryopreserved tumor specimens was evaluated using the enzyme-linked immunosorbent assay. The HSC-2 cells were treated with 2F10, a monoclonal antibody against CD44v6. The effects of 2F10 on HSC-2 cell proliferation, migration, and invasion potential were evaluated. RESULTS: The down-regulation of CD44v6 expression or the concentration of cancer tissue significantly correlated with a lower degree of pathohistological differentiation and a higher rate of cervical metastasis. The invasion of HSC-2 cells into type I collagen gel and the expression of CD44v6 were decreased in invading cells released from the upper layer. Furthermore, the treatment of HSC-2 cells with 2F10 significantly enhanced cell invasion. However, 2F10 did not affect either the proliferation or migration properties of HSC-2 cells. CONCLUSIONS: The down-regulation of CD44v6 expression may be useful as a biological marker for the degree of malignancy in HNSCCs. We assume that the loss or dysfunction of CD44v6 is involved in the acquisition of invasion ability in HSC-2 cells. In addition, the potential existence of a CD44v6-mediated signal transduction pathway may play a role in inhibiting the invasion in HNSCCs.