E-cadherin、β-catenin、CD44v6在乳腺癌中的表达

目的　探讨乳腺癌中E cadherin(E cad)、β catenin(β cat)、CD4 4v6蛋白表达。 方法　采用免疫组化S P法测定 4 8例乳腺癌中E cad、β cat、CD4 4v6蛋白的表达。 结果　E cad、β cat蛋白的表达强度 ,无淋巴结转移组高于有淋巴结转移组 (P <0 0 5 ) ,与肿瘤的大小、病理分级、组织学分类无关 ;在乳腺癌中随着E cad强度的增加 ,β cat阳性率亦呈上升趋势 (P <0 0 5 )。CD4 4v6蛋白的表达强度 ,有淋巴结转移组高于无淋巴结转移组 (P <0 0 5 ) ,与肿瘤的大小、病理分级、组织学分类无关。结论　E cad、β cat、CD4 4v6的表达可作为判断乳腺癌是否转移的可靠指标     

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。     

胆囊癌组织P62蛋白的表达及其与血管生成关系

目的 :检测胆囊癌组织中P6 2蛋白、碱性成纤维细胞生长因子(bFGF)的表达和微血管密度 (MVD) ,探讨它们的相互关系 ,以及与胆囊癌临床病理特征的关系。方法 :4 1例胆囊癌和 2 2例慢性胆囊炎组织中 ,P6 2蛋白和bFGF的表达用SP免疫组化染色法进行检测。胆囊癌组织中MVD用抗CD34单抗 (mAb)做SP免疫组化染色进行检测。结果 :4 1例胆囊癌组织中 ,P6 2和bFGF表达阳性率分别为 6 3.4 %和 75 .6 % ,均高于 2 2例慢性胆囊炎组织 (P <0 .0 1)。P6 2的表达与胆囊癌淋巴结转移有关 (P <0 .0 5 ) ,与癌组织的分级、临床分期无显著关系。bFGF的表达与胆囊癌临床病理分期及组织学分级有关 (P <0 .0 5 ) ,而与淋巴结转移无显著关系。P6 2表达率与bFGF表达率呈正相关关系 (r=0 .5 2 1;P <0 .0 1)。两者的表达均与患者的年龄、性别、肿瘤的种类、是否伴有胆囊结石无关。胆囊癌组织中MVD明显高于慢性胆囊炎组织 (P <0 .0 1)。P6 2及bFGF表达阳性组织MVD高于表达阴性组织 (分别P <0 .0 5和P <0 .0 1)。MVD与胆囊癌的Nevin分期及淋巴结转移有关 (P<0 .0 1) ,与患者的年龄、性别、肿瘤种类、分化程度以及是否伴有胆囊结石无关。结论 :P6 2蛋白及bFGF的表达与胆囊癌组织中血管的生成相关 ,在胆囊癌的发生和发展过程中可能具有重     

膀胱移行细胞癌中bax、bel-2、CD44v6、nm23表达

目的　探讨bax、bcl 2、CD4 4、nm2 3基因蛋白在膀胱移行细胞癌 (TCC)中的表达。方法　应用免疫组化S P法对 6 4例膀胱TCC及 2 0例正常膀胱黏膜组织中bax、bcl 2、CD4 4v6、nm2 3进行检测。结果　 6 4例膀胱TCC中bax阳性率为 17 2 % (11/6 4 ) ,正常膀胱黏膜组织为 90 0 % (18/ 2 0 ) (P <0 0 5 )。膀胱TCC中bcl 2阳性表达率为 82 8% (5 3/ 6 4 ) ,正常膀胱黏膜为 2 0 0 %(4 / 2 0 ) (P <0 0 5 )。bax、bcl 2阳性率随组织学分级的提高有逐渐增强的趋势 ,但无统计学意义 (P >0 0 5 ) ;在无浸润及有深层浸润的膀胱TCC中 ,bax的阳性表达率分别为 16 3%、2 0 0 % (P >0 0 5 ) ,bcl 2则分别为 83 7%、80 0 % (P >0 0 5 ) ;在无复发转移及有复发转移的膀胱TCC中 ,bax阳性率分别为 16 1%、2 5 0 % (P >0 0 5 ) ,bcl 2分别为 82 1%、87 5 % (P >0 0 5 )。 6 4例膀胱TCC中CD4 4v6阳性表达率为 5 0 0 % (32 / 6 4 ) ,正常膀胱黏膜组织为 5 0 % (1/ 2 0 ) (P <0 0 5 )。nm2 3在膀胱TCC中的阳性率为 76 6 % (4 9/ 6 4 ) ,正常膀胱黏膜组织为 2 0 0 % (4 / 2 0 ) (P <0 0 5 )。CD4 4v6阳性率Ⅰ、Ⅱ级与Ⅲ级相比差异有显著性 (P <0 0 5 ) ,nm2 3阳性率Ⅰ级与Ⅱ、Ⅲ级相比差异有显著性 (P <0 0     

肺癌组织中MDR1 mRNA、nm23H1 mRNA、P-gp和CD44v6的表达及其相关性

目的 :探讨肺癌组织中MDR1mRNA、nm2 3H1mRNA、P gp和CD44v6的表达及其与淋巴结转移、病理分型的相关性。方法 :应用原位杂交 (ISH)CSA法和免疫组化EnVision法检测 6 0例人原发性肺癌组织MDR1nm2 3H1mRNA、P gp和CD44v6的表达。结果 :MDR1mRNA、nm2 3H1mRNA、P gp混合单抗和CD44v6的阳性率分别为 46 6 7% (2 8/ 6 0 )、5 3 33 % (32 / 6 0 )、5 1 6 7% (31/ 6 0 )和 6 3 33% (38/ 6 0 )。不同克隆P gp阳性率分别为JSB 133 33% (2 0 / 6 0 ) ,C2 1931 70 % (19/ 6 0 )和C49416 70 % (10 / 6 0 )。nm2 3H1mRNA与肺癌的第一站和第二站淋巴结转移呈负相关 (P <0 0 1,P <0 0 5 ) ,而CD44v6呈正相关(P <0 0 1,P <0 0 1)。MDR1mRNA和P gp与CD44v6的阳性表达关系密切 (P <0 0 1) ,并与肺癌患者吸烟关系密切 (P <0 0 1)。MDR1mRNA和P gp的阳性符合率为 80 6 4% (2 5 / 31)。 结论 :IHC方法检测P gp能间接反映MDR1mRNA的转录水平 ,为准确评估肺癌病人对化疗的疗效提供一种有效手段 ,MDR的表达与病人吸烟关系密切     

c-erbB-2过表达、nm23低表达与结直肠癌预后不良的关系

目的　探讨结直肠癌c erbB 2、CD4 4v6、nm2 3基因蛋白表达与临床病理特征的相关性及意义。方法　用免疫组织化学SP法检测了 92例结直肠癌组织c erbB 2、CD4 4v6、nm2 3蛋白表达 ,并对其中随访 10年以上的 2 8例作了生存分析。结果　c erbB 2和CD4 4v6的表达均与国际抗癌联盟(UICC)分期有关 (P <0 0 5 ) ,而且c erbB 2表达还与显著的瘤周淋巴样细胞浸润有关 (P <0 0 5 )。在随访 10年以上的 2 8例中 ,单因素分析显示 :患者生存率与组织分型、UICC分期、肿瘤生长方式、瘤周淋巴样细胞浸润以及c erbB 2、CD4 4v6、nm2 3表达均有关。但经多因素Cox比例风险分析 ,只有UICC分期、c erbB 2和nm2 3表达具有独立的预后意义。结论　除UICCⅢ、Ⅳ期之外 ,c erbB 2过表达和nm2 3表达减少似乎可作为结直肠癌预后不良的可行性指标     

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。     

食管癌组织中多药耐药相关蛋白和CD44v6的表达

目的　探讨多药耐药相关蛋白 (multidrugresistance associatedprotein ,MRP)和CD44v6在食管癌组织中表达的意义 ,以及两者之间的关系。方法　采用免疫组织化学S P法检测 74例食管癌组织中MRP和CD44v6的蛋白表达。结果　MRP和CD44v6在食管癌组织中的阳性表达率分别为 5 1 4 %和 83 8%,食管癌中MRP的表达与肿瘤的浸润深度和淋巴结转移呈正相关 (P <0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。CD44v6在食管癌中的表达与肿瘤的浸润深度和淋巴结转移密切相关 (P <0 0 5 ) ,而与肿瘤的分化程度无关 (P >0 0 5 )。CD44v6在MRP阳性食管癌中的表达明显高于其在MRP阴性食管癌中的表达 (P <0 0 5 )。结论　肿瘤多药耐药可能与肿瘤转移有关 ,检测食管癌中MRP和CD44v6的表达可能反映肿瘤细胞的生物学行为。     

子宫内膜癌中β-连环素表达及与预后的关系

目的　探讨 β 连环素 (β catenin ,β Cat)在子宫内膜癌中的表达及与预后的关系。 方法　应用免疫组化S P法检测 2 0例正常子宫内膜 ,36例子宫内膜癌标本中 β Cat及靶基因c myc产物的表达。 结果　β Cat、c myc在子宫内膜癌组中阳性表达率分别为 5 2 8%、4 7 2 % ,显著高于正常子宫内膜组 (P <0 0 5 ) ;随着组织学分级的增加 ,β Cat阳性率显著上升 ,c myc表达也平行上升。G1级与G2 级间、Ⅰ期与Ⅱ期间差异有显著统计学意义 (P <0 0 5 ) ,且两者在子宫内膜癌中表达呈正相关 (r =0 4 990 ,P =0 0 0 6 ) ;有肌层浸润和淋巴结转移组 β Cat阳性率显著高于无肌层浸润和淋巴结转移组 (P <0 0 1) ;而c myc表达与肌层浸润和淋巴结转移无明显相关。结论　β Cat表达与预后呈负相关 ,是评估预后的有效参数     

非小细胞肺癌中Ezrin和CD44v6的表达及意义

目的 探讨非小细胞肺癌中Ezrin和CD44v6的表达及其与肺癌各种临床病理参数之间的关系.方法 采用免疫组化SP法检测55例非小细胞肺癌组织中Ezrin及CD44v6的表达.结果 Ezrin的表达程度与非小细胞肺癌的TNM分期(P=0.004)和淋巴结转移(P=0.003)密切相关; CD44v6的表达程度与非小细胞肺癌的TNM分期(P=0.012)和淋巴结转移(P=0.010)密切相关;Ezrin 和CD44v6两者在非小细胞肺癌组织中的表达呈正相关(r=0.568, P=0.000).结论 Ezrin和CD44v6与肺癌淋巴结转移和临床TNM分期密切相关,联合检测Ezrin和CD44v6有助于判断肺癌的预后.     

CD44s and CD44v6 expression in localized T1-T2 conventional renal cell carcinomas

To assess the prognostic value of CD44s and CD44v6 tumour expression for patients with T1-T2 conventional renal cell carcinomas, a retrospective immunohistochemical analysis of 95 patients was undertaken. These patients had undergone a radical nephrectomy, performed in three institutions in France between 1987 and 1993. The mean age of the patients was 62.9+/-10.2 years (range from 37 to 85 years) with 66.3% males. At the time of surgery, 84 patients had a T1 and 11 a T2 renal tumour. Fuhrman nuclear grading showed 44 (46.3%) tumours of grade 1, 39 (41.1%) of grade 2, and 12 (12.6%) of grade 3. The mean follow-up period was 58.1+/-36.1 months. At the end of follow-up, eight patients (8.4%) had metastatic disease and no local recurrence was seen. Immunohistochemistry showed that 26 tumours (27.4%) expressed CD44s, but none expressed CD44v6. Statistical analysis showed that CD44s expression was correlated with tumour size (p=0.006) and Fuhrman grading (p<10(-4)). Among the various parameters tested for the multivariate analysis, CD44s expression correlated only with disease-free survival (p=0.04). It is concluded that CD44s expression, but not CD44v6, is of potential prognostic interest in patients with localized T1-T2 conventional renal cell carcinomas.     

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

Yoo S H, Lee K, Chae J Y & Moon K C
(2011) Histopathology  58 , 191–197
CD151 expression can predict cancer progression in clear cell renal cell carcinoma Aims: CD151 is known to be implicated in cancer progression and metastasis. The aim was to evaluate the expression of CD151 in clear cell renal cell carcinoma (CCRCC) and to assess its prognostic significance. Methods and results: The expression of CD151 was evaluated in 489 cases of CCRCC by immunohistochemistry. Immunoreactivity was classified into four categories (minimal, 0–10% positive cells; focal, 10–50% positive cells; diffuse moderate, >50% positive cells with moderate staining intensity; diffuse strong, >50% positive cells with strong staining). To determine the statistical significance of CD151 expression in CCRCC, all cases were divided into two groups based on their CD151 expression level: a CD151‐low group (n = 257; minimal and focal) and a CD151‐high group (n = 232; diffuse). Expression of CD151 was correlated positively with pT, pN, pM categories, pathological tumour–node–metastasis (pTNM) stage, nuclear grade, tumour size and patient’s age. The CD151‐high group had significantly shorter cancer‐specific survival (P < 0.001) and progression‐free survival (P < 0.001) times. Furthermore, multivariate analysis showed that CD151 expression was an independent predictor for tumour progression in patients with CCRCC (P = 0.040). Conclusions: High CD151 expression is associated with advanced stage and high nuclear grade in CCRCC. CD151 is a prognostic marker for tumour progression in CCRCC patients.     

Expression of CD9 and CD82 in clear cell renal cell carcinoma and its clinical significance

CD9 and CD82, members of the tetraspanin family, act as metastasis suppressors in many human malignant tumors, but the role of these molecules is not well known in clear cell renal cell carcinoma (CCRCC). This study was designed to evaluate the immunohistochemical expression of CD9 and CD82 in 644 cases of CCRCC and to determine the clinicopathologic and prognostic significance of their expression. The percentage of positive tumor cells was evaluated, and the expression was classified into 2 categories: low expression (less than 10% positive cells) or high expression (more than 10% positive cells) for CD9 expression and negative (no positive cells) or positive for CD82 expression. CD9 high expression was found in 303 (47.0%) patients, and CD82 positivity was found in 98 (15.2%) patients. High expression of CD9 was statistically associated with older patients (p = 0.003). The cases showing positive immunoreactivity for CD82 exhibited a high stage (p < 0.001) and high nuclear grade (p < 0.001). The overall, cancer-specific and progression-free survival rates were significantly higher in patients with a CD82-negative profile compared to patients with a CD82-positive profile (p < 0.001). Although the biological function of CD82 in CCRCC remains unclear, the CCRCC patients with CD82 positive expression show poor prognosis.     

Reduced CD44 standard expression is associated with tumour recurrence and unfavourable outcome in differentiated thyroid carcinoma

CD44 was detected with an antibody recognizing all forms of CD44 (CD44 standard) and others specific for its v3 and v6 variant isoforms; their prognostic value was evaluated in 213 patients with differentiated thyroid carcinoma (DTC). The staining patterns of CD44 standard (s) and CD44v6 in tumour tissue were quite similar, 176 cases (83%) being highly positive for CD44s and 153 cases (72%) for CD44v6. Only 18 (9%) tumours showed high expression of CD44v3. Papillary carcinomas were significantly more often high expressors of CD44s and CD44v6 than follicular carcinomas (p<0.001 for both). Age older than 60 years, distant metastases, and advanced pTNM stage were related to loss of expression of CD44s (p<0.001, p=0.021, and p=0.003, respectively). Tumour recurrence and cancer-related mortality were related to the reduced level of CD44s (p=0.049 and p=0.042). CD44v3 did not associate with any of the clinicopathological factors. In univariate analysis, CD44s was the only significant prognostic factor for disease-free survival (p=0.0488). In multivariate analysis, CD44s and thyroglobulin level were significant prognostic factors for disease-free survival (p=0.040 and p<0.001, respectively). The reduced level of CD44s in DTC patients seems to be an independent prognostic factor for unfavourable disease outcome.     

Expression of Opa interacting protein 5 (OIP5) is associated with tumor stage and prognosis of clear cell renal cell carcinoma

Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, the biological function and clinical significance of OIP5 in human Clear Cell Renal Cell Carcinoma (CCRCC) remains unknown. In the present study, we found the expression of OIP5 was markedly upregulated in surgical CCRCC specimens and CCRCC cell lines. Immunohistochemical analysis revealed that paraffin-embedded archival CCRCC specimens exhibited higher levels of OIP5 expression than normal renal tissues. Further statistical analysis suggested the upregulation of OIP5 was positively correlated with the Fuhrman grade (P = 0.02), T classification (P = 0.015), N classification (P = 0.018) and clinical stage (P = 0.035). Also, patients with high OIP5 expression dramatically exhibited shorter survival time (P = 0.001). In addition, the OIP5 expression was an independent prognostic marker of overall survival of CCRCC patients in a multivariate analysis (P = 0.008). Experimentally, we demonstrated that silencing OIP5 in CCRCC cell lines by specific siRNA clearly inhibited cell growth. In conclusion, our findings suggested that OIP5 could be a valuable marker of CCRCC progression and prognosis, and a promising therapeutic target for CCRCC.     

CD44s and CD44v6 in diagnosis and prognosis of human bladder cancer

The cell adhesion molecules (CAMs) CD44 standard (CD44s) and its variant 6 (CD44v6) are involved in the progression and invasion of human malignancies. However, discrepancies in the prognostic value of CD44s and CD44v6 expression need to be addressed. Aims: To investigate the expression of CD44s and CD44v6 in bladder carcinomas and relate the results to the established prognostic factors. Materials and Methods: 50 bladder carcinoma specimens, 30 cases with transitional cell carcinoma (TCC: 6 bilharzial and 24 nonbilharzial) and 20 cases with squamous cell carcinoma (SCC: 8 bilharzial and 12 nonbilharzial), were included. Immunohistochemical analysis for CD44s and CD44v6 was carried out using avidin-biotin peroxidase method. Results: The level of both CD44s and CD44v6 in TCC was significantly higher in invasive than in preinvasive tumors and normal urothelium (p < .05). A direct association between the percentage of expression of both markers and the grade of TCC (p < .05) was observed. An inverse correlation between CD44s and SCC was seen, where metaplastic urothelium showed higher expression than invasive carcinomas. No association was observed between the expressions of both CD44s and CD44v6 and bilharzial ova, sex and age of the patient, or size of the tumor. Conclusions: The authors report statistically significant correlation between CD44s and CD44v6 expression and increasing grade and stage of TCC. No such correlation with SCC and with bilharzial cystitis, sex and age of the patient, or size of the tumor was documented.     

透明细胞肾细胞癌中cIAP1、cIAP2、XIAP的表达及其与临床指标的关系

目的：检测肾透明细胞癌中凋亡抑制蛋白cIAP1、cIAP2和xIAP基因表达状况及其与,临床病理指标间的关系。方法：采用RT-PCR方法检测cIAP1、cIAP2和XIAP在透明细胞肾细胞癌中RNA水平的表达。分析其与透明细胞肾细胞癌,临床病理指标间的关系。结果：在透明细胞‘肾细胞癌中cIAP1和cIAP2的mRNA阳性率分别为85％（17／20）和60％（12／20）,均高于正常肾组织。cIAP1 mRNA在Fuhrman核分级1、2级的肾细胞癌中表达高于核分级3和4的肿瘤。XIAP的表达在肾细胞癌与癌旁正常肾组织间无差异,并与TNM分期、Fuhrman分级没有相关性。结论：IAP家族成员cIAP1与肾细胞癌的临床病理指标相关。     

Orai1 Expression Is Closely Related with Favorable Prognostic Factors in Clear Cell Renal Cell Carcinoma

Store-operated calcium (Ca²⁺) entry (SOCE) is the principal Ca²⁺ entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients’ outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.     

Expression of CD44 standard and variant-v6 proteins in transitional cell bladder tumours and their relation to prognosis during a long-term follow-up

The expression of the standard CD44 (CD44s) and its v6 isoform (CD44v6) was analysed immunohistochemically in 173 cases of transitional cell bladder cancer. The results of immunohistochemical analyses were related to established prognostic factors and clinical follow-up data. The expression intensity of CD44s in non-basal tumour cells was significantly related to TN classification, S-phase fraction (SPF), mitotic index, grade, density of tumour infiltrating lymphocytes. The expression intensity of CD44v6 in non-basal tumour cells was inversely related to DNA ploidy, SPF, and mitotic index. The expression intensity of CD44v6 in basal tumour cells was also inversely related to T-category, grade, papillary status, DNA ploidy, SPF, and mitotic index. Strong expression of CD44s in non-basal tumour cells was related to unfavourable outcome in univariate analysis (p=0·008), whereas the strong expression of CD44v6 in both non-basal cells (p=0·005) and basal cells (p=0·0008) was related to high survival probability. In multivariate survival analysis, the expression intensity of CD44v6 was independently related to favourable outcome in muscle invasive tumours, while in superficial tumours, CD44s was an independent prognostic factor. The results suggest that the expression of CD44s and CD44v6 is associated with malignant features and prognosis in bladder cancer. Copyright © 1998 John Wiley & Sons, Ltd.