CD44s和CD44v6在宫颈鳞癌中表达及其临床意义

目的：探讨宫颈鳞癌中CD44s和CD44v6的表达及其与临床病理资料的关系。方法：应用免疫组化EnVision两步法对31例宫颈鳞标本中CD44s和CD44v6蛋白表达并进行分析。结果：肿瘤原发灶中CD44s阳性表达率为61．3％（19／31）。CD44v6阳性表达率为93．5％（29／31）,CD44v6阳性率高于CD44s,CD44s阳性表达与临床分期,病理分级和分类无关（P＞0．05）,CD44v6阳性表达与肿瘤细胞分化程度无关,但与浸润程度及分期有关（P＜0．05）,结论：CD44v6基因蛋白与宫颈鳞癌的侵袭,转移相关,可作为预测肿瘤进展和预后的一种有用指标。     

Ki-67和CD44v5在卵巢癌中的表达和临床意义

目的 研究ki-67和CD44v5在卵巢癌中的表达及临床意义。方法 用免疫组化sp法研究ki-67和CD44v5在40例卵巢癌手术切除标本及10例卵巢上皮良性肿瘤中的表达。结果 40例卵巢癌中，ki-67和CD44v5的阳性表达率分别为77．5％和47．5％，远高于在卵巢上皮良性肿瘤中的表达30．0％和20．0％。且随着肿瘤病理分化程度的降低，ki-67、CD44v5阳性表达率均呈增高趋势；ki-67在卵巢腺癌中的阳性表达率明显高于透明细胞癌、内膜样癌（P〈0．05）；CD44v5的阳性表达率与表达强度伴淋巴转移者显著高于无淋巴转移者（P〈0．01）；两者呈正相关。结论 ki-67和CD44v5在卵巢癌中的表达对卵巢癌的诊断、治疗方式的选择、手术范围的确定、及术后防治复发、化疗药物的应用，具有重要的指导意义。     

肺腺癌细胞微环境及转移与黏附分子表达的关系

目的研究肺腺癌细胞生长环境及转移性与黏附分子CD44v6和CD29的表达关系。方法将起源相同、转移性不同的两个肺腺癌细胞系AGZY和Anip分别用简便肿瘤多细胞球体(MTS)培养法培养，并设常规单层贴壁细胞培养对照。通过倒置显微镜、扫描及透射电镜观察MTS形成情况，并用免疫组化法分别对MTS及贴壁细胞上CD44v6和CD29表达进行检测。结果MTS培养成功，贴壁细胞与MTS在细胞结构及细胞连接结构上相似，两种MTS在形态及结构上差异无显著性。免疫组化结果显示，CD29在高转移性的Anip细胞及其MTS上呈阳性表达；在低转移性的AGZY细胞及其MTS上阴性表达。CD44v6在Anip和AGZY细胞及MTS上均呈阳性表达，差异无显著性。贴壁细胞与MTS上两种黏附分子表达均无差异。结论成功建立了一种简易制备MTS的方法。细胞生长方式(单层贴壁与MTS)可能不影响CD44v6和CD29的表达。CD29表达可能与肺腺痛转移性相关；CD44v6表达可能与肺腺癌转移无关。     

Survivin和CD44v6在子宫内膜异位症中的表达及意义

目的研究Survivin、CD44v6在卵巢子宫内膜异位症中的表达，以探讨二者与卵巢子宫内膜异位症发病的关系。方法用免疫组化S-P方法检测卵巢子宫内膜异位症31例异位内膜、5例在位内膜、15例正常内膜中Survivin和CD44v6的表达。结果Survivin蛋白在异位内膜中表达明显高于在位内膜、正常内膜（P〈0．05）；CD44v6蛋白在异位内膜组与增生期内膜比较有统计学意义（P〈0．05），与其他两组比较无统计学意义（P〉0．05）；二者的表达不随AFS分期的变化而变化；并且二者在卵巢子宫内膜异位症中的表达呈相关性（r=0．24），但无统计学意义（P〉0．05）。结论Survivin和CD44v6在卵巢子宫内膜异位症中的异常表达对卵巢子宫内膜异位症的发生及发展起着重要的作用.     

上皮型钙黏附蛋白、CD44v6及连接蛋白43在肝细胞癌中的表达及意义

目的研究上皮型钙黏附蛋白（E-cad）、CD44v6和连接蛋白43（Cx43）在人肝细胞癌（HCC）中的表达及其表达与患者性别、年龄和组织学分级的关系。方法采用免疫荧光双标记染色技术结合激光扫描共聚焦显微镜观察E—cad、CD44v6及Cx43在30例正常肝组织,25例肝良性病变和38例HCC中的表达;另在HCC组检测并分析了该3种标记物的表达与性别、年龄和组织学分级的关系。结果E—cad与Cx43均在正常肝组织及肝良性病变组高表达,而在HCC组表达都明显降低,前两组与HCC组问表达强度差异均有统计学意义（FE-cad=879．2,F Cx43=303．7,P〈0．05）。相反,CD44v6在正常肝组织及肝良性病变组表达较低,而在HCC中表达较高,差异有统计学意义（F=2057．2,P〈0．05）。HCC组E—cad和Cx43阳性表达强度在患者不同性别、年龄及肿瘤的组织学分级问的差异均无统计学意义（P〉0．05）;而CD44v6表达与HCC的组织学分级有关,HCC分化差,CD44v6表达高（t=-2．06,P〈0．05）,但不同年龄、性别组HCC的CD44v6阳性表达强度差异无统计学意义（P〉0．05）。HCC组E—cad与Cx43的表达呈正相关,而E—cad、Cx43与CD44v6的表达呈负相关。结论HCC的发生、发展伴随着多种分子表型的改变。E—cad、Cx43的低表达与CD44v6的高表达可能参与HCC的侵袭,尤其是CD44v6的表达还与HCC的组织学分级相关。三者联合检测对判断HCC的诊断和预后有一定价值。     

CD15 mRNA在原发性肝细胞癌中的表达及其预后意义

目的：研究CD15mRNA表达与原发性肝细胞癌（HCC）侵袭转移和预后关系及与CD44v6和nm23H1的mRNA表达相关性。方法：应用原位杂交和免疫组织化学方法，检测分析HCC组织中CD15mRNA及其蛋白、CD44v6及nm23H的mRNA表达。结果：99例HCC中，CD15mRNA及其 蛋白、CD44和nm23H1的mRNA表达阳性率分别为38．4％、36．7％、41．4％和76．8％。CD15mRNA表达与其 蛋白表达一致，与CD44v6 mRNA表达呈正相关，与nm23H1 mRNA表达呈负相关。CD15mRNA及其蛋白、CD44和nm23H1的mRNA表达均与HCC侵袭转移倾向和患者预后相关。结论：检测CD15表达有可能成为HCC侵袭转移和预后判断的一项新的病理生物学指标。     

套细胞淋巴瘤免疫表型的变异

套细胞淋巴瘤根据形态特征可分为经典型和变异型.经典型主要表现为中小淋巴细胞单一性增生、不规则核和核仁不明显;变异型主要包括母细胞性套细胞淋巴瘤和多形性套细胞淋巴瘤,临床表现通常具有更强的侵袭性.套细胞淋巴瘤的免疫表型为表达全B细胞抗原和细胞周期蛋白D1(cyclin D1),通常CD5+、CD10-、CD23-和FMC7+.     

凝集素受体和抗角蛋白单克隆抗体在宫颈储备细胞癌变研究中的应用

本文用生物素化12种凝集素和抗角蛋白单克隆抗体K27、K174去标记不同宫颈病变诊断组织,了解宫颈储备细胞增生、分化及其在鳞癌和腺癌癌变过程中,细胞浆、细胞膜、细胞核12种凝集素受体表达情况,及其宫颈储备细胞增生、不成熟鳞化、成熟鳞状化生、非典型增生和宫颈癌组织抗角蛋白单克隆抗体K27、K174阳性表达     

Ezrin在转移性骨肿瘤中的表达及其与CD44V6表达的相关性

目的探讨人体转移性骨肿瘤组织中Ezrin和CD44v6表达之间的关系及Ezrin mRNA的表达与转移性骨肿瘤临床病理特征的关系。方法收集28例转移性骨肿瘤和12例良性骨肿瘤,应用免疫组织化学技术检测Ezrin和CD44v6的蛋白表达,应用RT-PCR检测Ezrin mRNA的表达情况。结果转移性骨肿瘤中Ezrin、CD44v6的蛋白阳性表达显著高于它们在良性骨肿瘤中的阳性表达(P<0.05);Ezrin和CD44v6的表达呈正相关(r=0.053,P<0.05);Ezrin mRNA的阳性表达与患者性别、年龄、有无原发灶和转移瘤部位无关,但与其分化程度有关。结论 Ezrin可能参与了转移性骨肿瘤的浸润、转移;Ezrin发挥作用可能需要与细胞粘附分子CD44v6相互作用;检测Ezrin的表达可作为转移性骨肿瘤生物学行为的一项评估指标。     

CD44v6和E-cadherin表达与结直肠癌浸润转移关系

目的　探讨CD44v6和E cadherin(E cad)蛋白表达与结直肠癌浸润转移的相关性。方法　应用免疫组织化学技术 ,检测 90例结直肠癌组织中CD44v6和E cad蛋白表达。结果　 90例结直肠癌中CD44v6和E cad蛋白阳性表达率分别为75 6 %和 46 7%。CD44v6高表达及E cad低表达与结直肠癌Dukes分期、浆膜浸润、淋巴结转移、肝脏转移均呈正相关 (P <0 0 5 )。结直肠癌中CD44v6表达与E cad表达呈负相关 (r =- 0 4 3,P <0 0 0 5 )。结论　CD44v6和E cad表达与结直肠癌浸润转移密切相关。检测CD44v6和E cad蛋白表达可作为判断结直肠癌预后的客观指标。     

Relationship between CD44 expression and cell proliferation in epithelium and stroma of colorectal neoplasms.

The cell surface glycoprotein CD44 is expressed primarily in the region of cell replication in the lower crypt epithelium of colorectal mucosa, and its expression is markedly increased in colorectal neoplasms, suggesting that expression is linked to proliferation. The association between CD44 expression and replication in individual cells was therefore analyzed by double-label immunohistochemistry for CD44 and the cell-cycle-dependent protein proliferating cell nuclear antigen (PCNA). Enhanced expression of CD44 in colorectal neoplasms occurred not only in epithelial cells but also in stromal cells, including lymphocytes and macrophages. On a topographical basis, the cellular localization of CD44 and PCNA were commonly different. Quantitatively, in all cell types studied (epithelial cells and stroma of colorectal mucosa, adenomas, and carcinomas) PCNA was present most frequently in cells lacking CD44. Statistical analysis by logistic regression models indicated that cells negative for CD44 had a higher probability of being positive for PCNA than did cells positive for CD44 (P < 0.001). These data suggest that the enhanced level of CD44 in colorectal neoplasms is asynchronous with cell replication and reflects mechanisms that act on nonproliferative stromal lymphocytes and other mononuclear cells as well as the epithelial cells.     

宫颈癌PCNA和PTEN的表达与癌细胞增殖及淋巴结转移的关系

目的研究增殖细胞核抗原(PCNA)、抑癌基因PTEN在宫颈癌中表达与癌细胞增殖及淋巴结转移的关系。方法应用免疫组化SP法检测40例宫颈良性病变及68例宫颈癌中PCNA、PTEN的表达。结果PCNA在宫颈癌组织中的阳性表达率显著高于宫颈良性病变的表达(P0.01),与淋巴结转移呈正相关(P0.05)。PTEN蛋白表达率显著低于宫颈良性病变的表达(P0.01),与淋巴结转移呈负相关(P0.05)。PTEN在宫颈癌中的表达与PCNA呈负相关(P0.01)。结论PTEN失活或蛋白表达降低与癌细胞增殖及淋巴结转移密切相关,宫颈癌PCNA表达增强而PTEN表达降低,其癌细胞增殖活跃。联合检测PCNA、PTEN,有助于提高宫颈癌侵袭转移能力的评估,对指导临床治疗和估计预后有重要意义。     

Expression of CD44s, CD44v6, and hyaluronan across the spectrum of normal-hyperplasia-carcinoma in breast.

BACKGROUND: The interaction between transmembrane receptors on epithelial tumor cells and the surrounding extracellular matrix molecules is important in tumor progression and metastasis. This interaction is best exemplified by the relationship of the receptor CD44 and the extracellular matrix component hyaluronan (HA). This study seeks to evaluate the expression and the correlation of CD44s, CD44v6, and HA in normal, hyperplastic, and malignant breast epithelium and stroma. MATERIALS AND METHODS: Archival paraffin-embedded tissue from cases of normal breast tissue (n=10), intraductal hyperplasia without atypia (n=13), ductal carcinoma in situ (DCIS) (n=24), stage I infiltrating ductal carcinoma (n=28), stage II infiltrating ductal carcinoma (n=31), and their corresponding positive lymph nodes were retrieved from the surgical pathology files. Tissue sections were evaluated for the expression of CD44s, CD44v6, and HA in the epithelial and stromal cells by immunohistochemistry. RESULTS: Ductal epithelial cells and myoepithelial cells expressed CD44s in all cases of normal and benign breast tissue. The expression of CD44s in breast epithelium progressively decreased with increasing deviation from normal histology: 83% in DCIS, 46% in stage I ductal carcinoma and 26% in stage II ductal carcinoma. The reverse trend was observed for CD44v6 in ductal epithelium: 0% in normal breast, 15% in intraductal hyperplasia, 100% in DCIS, 82% in stage I infiltrating ductal carcinoma, 94% in stage II carcinoma, and 100% of metastatic carcinoma in the lymph nodes. HA was noted exclusively in the stroma but not in the epithelial cells. HA was faintly expressed in the intralobular stroma of normal breast tissue, confined to a narrow faint band adjacent to intraductal hyperplasia and localized to a broad well-defined band around DCIS. Stromal HA staining was more diffuse and intense in infiltrating carcinomas and was particularly pronounced surrounding the metastatic deposits in lymph nodes. CONCLUSIONS: This study demonstrates decreased expression of CD44s accompanied by increased expression of CD44v6 and increased stromal HA in breast cancer. These findings suggest that CD44s, CD44v6, and HA play complementary roles in the development and progression of breast cancer.     

Expression of CD 44 s, CD 44 v 3 and CD 44 v 6 in benign and malignant breast lesions: correlation and colocalization with hyaluronan

AIMS: To examine the expression of CD 44 s, CD 44 v 3 and CD 44 v 6 in breast lesions, and to correlate it with the expression of hyaluronan (HA). Methods and results: CD 44 expression was studied in 75 breast tissue samples, consisting of benign, premalignant and malignant breast lesions, using immunohistochemistry. CD 44 s, but not CD 44 v 3 or CD 44 v 6, was found in the stromal cells, and it was similar in benign and malignant tumours. In benign lesions CD 4 v 6 was detected in 20-30% of the ductal epithelial cells, while C 44 v 3 and CD 44 s were not expressed. CD 44 s, CD 44 v 3 and CD 44 v 6 were all up-regulated in the in situ carcinomas and invasive carcinomas. The level of CD 44 expression in carcinoma cells did not correlate with the type or differentiation of the tumours. CD 44 and HA expression levels were not closely linked in the benign or malignant breast lesions, because HA was overexpressed later in breast cancer progression than CD 44. However, in breast carcinomas CD 44 and HA positivity was often found in the same areas of the sections, and the dual staining confirmed actual colocalization of CD 44 s and HA in the same cells. Conclusions: CD 44 s, CD 44 v 3 and CD 44 v 6 are up-regulated earlier than HA in breast carcinoma progression, and in later stages they often colocalize with cell surface HA.     

Enhanced expression of CD44 variants in human atheroma and abdominal aortic aneurysm: possible role for a feedback loop in endothelial cells

CD44, a polymorphic hyaluronate receptor, may participate in chronic inflammation. We hypothesized that CD44 variants contribute to the development of arterial diseases. CD44 levels vary in normal and diseased arterial tissues in the following order: unaffected arteries < fibrous plaques < or = abdominal aortic aneurysm < atheromatous plaques; and correlate with macrophage content. Furthermore, plaque microvessels express CD44, and anti-CD44v3 or anti-CD44v6 treatment reduces endothelial cell proliferation but not apoptosis in vitro, suggesting functionality of these receptors. Endothelial cells express CD44H and CD44v6 after exposure to interleukin-1beta and tumor necrosis factor-alpha. Macrophages, a major source of abundant CD44 in vitro, express not only CD44H but also variants CD44v4/5, CD44v6, and CD44v7/8, isoforms distinctively regulated by proinflammatory cytokines. Several proinflammatory cytokines induce shedding of CD44 from the surface of macrophages and endothelial cells. Soluble CD44 stimulates the expression and release of interleukin-1beta from endothelial cells, suggesting a positive feedback loop of this cytokine. By demonstrating augmented expression of CD44 and variants within human atheroma and in abdominal aortic aneurysm as well as the vascular cell release of sCD44, a process regulated by proinflammatory cytokines, this study provides new insights on the functions of CD44 in arterial diseases.     

EXPRESSION OF CD44 SPLICE VARIANTS IN SQUAMOUS EPITHELIA AND SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK

Splice variants of the adhesion molecule CD44 have been described as essential for the lymphatic spread of rat tumour cells and are claimed to be involved in the metastatic spread of several human tumours. Immunohistochemistry has been used to analyse the expression pattern of CD44 standard (CD44s) and variant (CD44v) isoforms in normal and dysplastic squamous epithelia, as well as in primary and metastatic squamous cell carcinomas (SCCs), which spread predominantly by way of the lymphatic system. Frozen sections of squamous epithelia and of squamous cell carcinomas were stained with a panel of monoclonal antibodies recognizing epitopes of CD44s as well as of the variant exons v5, v6, v7, v7–v8, and v10. The stratum basale and stratum suprabasale of squamous epithelia stained with all antibodies; the stratum spinosum stained with anti-CD44v5, anti-CD44v6, anti-CD44v7–8 and anti-CD44v10; the lower layers of the stratum corneum stained with anti-CD44v5. This expression profile was seen in epithelia of the lip, the tongue, the gingiva, the hard palate, the floor of the mouth, the buccal mucosa, and the pharynx. The same pattern of expression was also noted in dysplastic epithelia, but expression of the variant exons v7, v8, and v10 was significantly downregulated in primary squamous cell carcinomas and was not detected at all in the majority of metastasis-derived specimens. Expression of CD44v5 and CD44v6, on the other hand, was mainly unaltered. Thus, epithelial cell layers representing different stages of differentiation express distinct sets of CD44 variant isoforms, where especially exons v8–v10 might be required for the maintenance of the structural integrity of squamous epithelium. Downregulation of these exons on tumour cells could indicate that they are irrelevant for tumour progression or may even hamper infiltration of surrounding tissue or of lymphatics.     

CD44v6与MMP—9在口腔鳞癌中的表达意义

目的：探讨细胞粘附分子CD44v6和基质金属蛋白酶MMP－9相互关系及其在评估口腔鳞癌的组织学分级,肿瘤浸润以及转移等生物学特性中的意义。方法：运用免疫组化S－P法测定22例口腔鳞癌和6例正常口腔黏膜组织中CD44v6和MMP－9的表达,结果：CD44v6在正常口腔黏膜组织呈强阳性表达;癌组织中CDv6的表达明显弱于正常组织,高表达CD44v6的口腔鳞癌不仅分化程度较差而且易发生淋巴结转移,MMP－9在正常口腔黏膜组织中呈阴性或弱阳性表达,癌组织中MMP－9的阳性表达高达68．2％（15／22）。MMP－9的表达与病理分级和颈淋巴结转移呈正相关（P＜0．05）,口腔鳞癌中MMP－9与CD44v6的表达呈正相关（P＜0．01）,多因素分析示两者之间的交互作用是影响口腔鳞癌病理分化和颈淋巴结转移的最重要因素。结论：口腔鳞癌中CD44v6与MMP－9的表达密切相关。MMP－9和CD44v6可作为临床上评估口腔鳞癌浸润,转移以及预后的指标。     

Expression of hyaluronic acid and its receptors, CD44s and CD44v6, in normal, hyperplastic, and neoplastic endometrium

The interaction between epithelial tumor cells and their surrounding stroma is important in tumor progression and metastasis. This is accomplished through a number of transmembrane receptors that interact with stromal extracellular matrix molecules. One of these receptors, CD44, binds to extracellular matrix component hyaluronic acid (HA). The purpose of this study was to evaluate the significance of HA, CD44s, and CD44v6 in benign, hyperplastic, atypical, and malignant endometrial epithelia. Archival paraffin-embedded cell blocks from proliferative endometrium (n = 11), secretory endometrium (n = 12), simple hyperplasia (n = 13), complex hyperplasia without atypia (n = 9), complex hyperplasia with atypia (n = 17), and adenocarcinoma (n = 21) were stained for HA, CD44s, and CD44v6. HA was detected throughout the normal menstrual cycle but was more intense during the secretory phase. Only during the secretory phase was CD44s expressed in the stromal cells in 11 cases (92%), whereas CD44v6 was detected in glandular epithelium in 9 (75%). CD44s was expressed in the glandular epithelium in 2 (15%) cases of simple hyperplasia, 4 (44%) of complex hyperplasia without atypia, 14 (82%) of complex hyperplasia with atypia, and in 16 (76%) of adenocarcinoma. CD44v6 was expressed in the glandular epithelium in 1 (11%) case of complex hyperplasia without atypia, 17 (100%) cases of complex hyperplasia with atypia, and in 18 (86%) cases of adenocarcinoma, but in none of the cases of simple hyperplasia. The endometrial stromal cells expressed CD44v6 in 1 (8%) case of simple hyperplasia, 6 (67%) of complex hyperplasia without atypia, 8 (47%) of complex hyperplasia with atypia, and in 3 (14%) of adenocarcinoma. We concluded that in the normal menstrual cycle, the timing of peak staining of HA and CD44s in the stroma and the up-regulation of CD44v6 in secretory glands are coincident with the period in which the endometrium is most receptive to embryo implantation. HA is more abundant in the stroma adjacent to the tumor, suggesting that interactions between tumor cells and stromal HA promote tumorigenesis. With progression from hyperplasia and with increasing atypia to adenocarcinoma, levels of stromal HA, glandular CD44v6, and glandular and stromal CD44s all increase. Thus, HA and CD44 are both involved in the development and progression of endometrial cancer.     

Diagnostic utility of CD44 standard, CD44v6, and CD44v3-10 expression in adenocarcinomas presenting in serous fluids.

CD44 is an 85 to 90 kd integral transmembrane protein encoded by a single 20-exon gene located on the short arm of chromosome 11. In the standard form (CD44s), 10 of the 20 exons are transcribed. Multiple variant isoforms exist (CD44v1-10) which arise from alternate mRNA splicing of the remaining 10 exons. In contrast to the standard form of CD44, which is almost ubiquitously expressed, splice variants are highly restricted in their expression in normal or malignant tissues. The purpose of this study was to evaluate the extent to which metastatic adenocarcinomas in effusions express CD44s, CD44v6, and CD44v3-10 and to assess their diagnostic utility in distinguishing reactive mesothelial cells from adenocarcinomas. Archival paraffin-embedded cell blocks of serous fluids from 23 cases of benign effusions containing reactive mesothelial cells and 45 cases of malignant effusions with metastatic adenocarcinoma (18 ovarian, 11 pulmonary, 9 gastrointestinal, and 7 breast) were retrieved from the surgical pathology files. The cytopathology of all cases was reviewed to confirm the diagnosis. Immunohistochemistry was performed on all cases using antibodies for CD44s, CD44v6, and CD44v3-10 (Bender MedSystems, CA). Positive staining was defined as distinct linear membrane staining. Strong staining in at least 10% of the tumor cells was required to consider the case positive for the particular marker. In benign effusions mesothelial cells expressed CD44s in 22 cases (96%), CD44v6 in 1 cases (4%) and CD44v3-10 in 0 cases (0%). In contrast neoplastic cells in malignant effusions expressed CD44s in 11 cases (24%), CD44v6 in 21 cases (47%), and CD44v3-10 in 39 cases (87%). We concluded that CD44s and CD44v3-10 are useful markers that can be applied to cytologic specimens. CD44s immunostaining can be used as a reliable marker to identify reactive mesothelial cells, meanwhile CD44v3-10 immunostaining can detect majority of adenocarcinomas in malignant effusions.