卵巢肿瘤粘附分子吞噬细胞糖蛋白的测定

目的：探讨卵巢肿瘤粘附分子吞噬细胞糖蛋白－１（ＣＤ４４）检测的方法和临床意义。方法：应用流式细胞免疫学方法，对１０６例不同性质及组织学类型的卵巢肿瘤患者外周血淋巴细胞粘附分子ＣＤ４４进行测定，并与健康妇女及卵巢非赘生物患者进行对照。结果：恶性肿瘤组术前淋巴细胞ＣＤ４４阳性率明显高于对照组及良性肿瘤组（Ｐ＜０．０１，Ｐ＜０．０５）；癌细胞ＣＤ４４阳性率高于自身外周血淋巴细胞（０．０１＜Ｐ＜０．０５）；卵巢癌不同组织类型的ＣＤ４４含量差异无显著性；术后外周淋巴细胞ＣＤ４４含量逐渐下降。结论：卵巢肿瘤组织及外周血淋巴细胞ＣＤ４４检测，对鉴别卵巢肿瘤性质、早期发现肿瘤复发和转移，有重要的临床价值。     

CD_(44)与肿瘤转移

ＣＤ４４是分布广泛的细胞表面糖蛋白，能与多种配体分子结合，参与细胞－细胞，细胞－基质之间的粘连。ＣＤ４４Ⅴ区外显子剪接方式的多样性及翻译后加工的复杂性导致ＣＤ４４蛋白具有庞大的异质性。现已发现，某些ＣＤ４４蛋白与肿瘤细胞的生长及转移有关。卵巢癌中ＣＤ４４Ｈ可能介导肿瘤腹腔内种植的过程。     

CD44与妇科肿瘤关系的研究进展

ＣＤ４４基因蛋白是一种细胞表面跨膜糖蛋白，能与透明质酸、层粘蛋白等基质分子结合，参与细胞－细胞、细胞－基质的粘连。近年研究发现ＣＤ４４参与肿瘤的浸润和转移。在宫颈癌、卵巢癌、外阴癌，ＣＤ４４Ｖ阳性者较阴性者有更强的恶性生物学行为，预后差，但在子宫内膜癌中结论相反。     

IL-2基因转移对卵巢癌细胞系SKOV3粘附性的影响

目的：研究ＩＬ－２基因转移对卵巢癌ＳＫＯＶ３细胞系粘附性的影响。方法：细胞对塑料基质、细胞基底膜成分的粘附实验,流式细胞术测定ＣＤ４４Ｈ的表达。结果：ＥＤＴＡ介导的细胞分离实验表明,ＳＫＯＶ３／ＩＬ－２细胞对塑料基质的粘附能力明显下降（Ｐ＜０．０１）;对基质及基底膜成分的粘附实验表明,ＳＫＯＶ３／ＩＬ－２细胞对Ⅳ型胶原和ｍａｔｒｉｇｅｌ的粘附能力下降,但对ＬＮ、ＦＮ的粘附能力无明显改变;粘附分子ＣＤ４４Ｈ的表达：ＳＫＯＶ３、ＳＫＯＶ３／Ｎｅｏ、ＳＫＯＶ３／ＩＬ－２组细胞粘附分子ＣＤ４４Ｈ阳性细胞百分率分别为７６．２％、６６．７％和３７．８％,ＳＫＯＶ３／ＩＬ－２组明显降低（Ｐ＜０．００１）。结论：ＩＬ－２基因修饰可使卵巢癌细胞系ＳＫＯＶ３粘附能力下降。     

CD44基因表达与妇科肿瘤

ＣＤ４４基因表达与妇科肿瘤曲焦书竹ＣＤ４４是分布极为广泛的细胞表面跨膜糖蛋白，属粘附分子家族，能与多种配体结合，参与细胞与细胞、细胞与基质间的粘连过程。近年来，因发现ＣＤ４４及其变异型（ＣＤ４４ｖ）在肿瘤细胞分化与转移过程中有重要作用，故倍受关注...     

c—erbB2反义核酸对卵巢癌细胞系生物学行为及药物敏感性的影响

目的：探讨ｃ－ｅｒｂＢ２反义核酸对卵巢癌细胞生物学行为及其化疗药物敏感性的影响。方法：应用ｐＵＣ－ｅｒｂＢ２和ｐＤＯＲ－ｎｅｏ质粒，构建了含反义ｅｒｂＢ２ｃＤＮＡ３．８ｋｂ的重组逆转录病毒表达载体ｐＤＯＲ－ｅｒｂＢ－ｎｅｏ，经脂质体转染ｅｒｂＢ２高表达的人卵巢癌细胞系ＳＫＯＶ３，再经Ｇ４１８（一种新霉素类似物）筛选得到新霉素抗性细胞，命名为ＳＫＯＶ３－Ａ２。结果：Ｓｏｕｔｈｅｒｎ印迹杂交分析表明，反义ｅｒｂＢ２３．８ｋｂ已完全整合到ＳＫＯＶ３细胞中，与亲本细胞及转染ｐＤＯＲ－ｎｅｏ的对照组细胞相比，ＳＫＯＶ３－Ａ２的生长和ＤＮＡ合成均受到抑制，且对５－氟尿嘧啶（５－ＦＵ）及顺铂（ＤＤＰ）的药物敏感性明显增加。结论：ｃ－ｅｒｂＢ２反义核酸在卵巢癌基因治疗中有一定作用；ｃ－ｅｒｂＢ２癌基因可能与卵巢癌细胞耐药有关。     

原癌基因C—myc,C—N—ras,C—Di—ras,C—erbB2在卵巢癌组织中的…

对３２例巢癌、４例卵巢良性上皮性肿瘤、３例卵巢上皮性交界性肿瘤及２例正常卵巢组织进行ＤＮＡＳｏｕｔｈｅｒｎ印迹杂交研究，发现在卵巢癌组织中原癌基因Ｃｍｙｃ，Ｃ－Ｎ－ｒａｓ和Ｃ－Ｋｉ－ｒａｓ，Ｃ－ｅｒｂＢ２扩增率分别为５０％、４４％、３１％、２５％。Ｃ－Ｋｉ－ｒａｓ扩增主要发生在早期和分化好的卵巢癌患者中。Ｃ－Ｎ－ｒａｓ扩增在晚期患者也有表现。Ｃｍｙｃ和Ｃ－ｅｒｂＢ２扩增主要发生在Ⅲ期以上、分化较差     

卵巢癌可溶性抗原和抗CD3单克隆抗体诱导细胞毒性T细胞抗人卵巢癌的实验研究

目的探讨卵巢癌过继细胞免疫治疗新方法。方法提取卵巢癌细胞（ＣＯＣ１和ＣＯＣ２ｎ）可溶性抗原（ＴＳＡ），用ＴＳＡ和抗ＣＤ３单克隆抗体（ＣＤ３ＭｃＡｂ）共同诱导正常人外周血单个核细胞（ＰＢＭＣ）产生细胞毒性Ｔ细胞（ＣＴＬ），用ＣＴＬ于体外杀伤ＣＯＣ１细胞和裸鼠体内抑制ＣＯＣ２ｎ移植瘤的生长，体外和淋巴因子激活杀伤细胞（ＬＡＫ）、淋巴因子和抗ＣＤ３单抗激活的杀伤细胞（ＣＤ３ＡＫ）细胞进行比较，体内和ＣＤ３ＡＫ细胞进行比较。结果ＣＴＬ、ＣＤ３ＡＫ和ＬＡＫ对ＣＯＣ１细胞的细胞毒作用分别为７９．４％、５２．１％和５１．７％（Ｐ＜０．０１）。在体内，ＣＴＬ与ＣＤ３ＡＫ和未经处理的对照组比较，卵巢癌细胞移植到裸鼠体内的第９天，肿瘤平均体积分别为４４．４±２４．２ｍｍ３、１１８．８±４０．０ｍｍ３和４４３．０±１５８．７ｍｍ３（Ｐ＜０．０１），裸鼠平均生存期分别为２８．５天、２５．５天和１７天（Ｐ＜０．０１）。结论本方法诱导产生的ＣＴＬ，在体内、体外对卵巢癌细胞均有较高的细胞毒作用，能明显抑制肿瘤生长，为卵巢癌治疗提供了新的思路。     

CD44S在卵巢肿瘤中的表达

ＣＤ４４Ｓ在卵巢肿瘤中的表达曲焦书竹陈斌其师宜荃张新莹郭月梅ＣＤ４４是一类分布极为广泛的细胞表面跨膜糖蛋白，主要参与细胞－细胞、细胞－基质间特异性粘连过程［１］。特别是ＣＤ４４标准型（ＣＤ４４Ｓ），是透明质酸（ＨＡ）的主要表面受体［２］，能介导细...     

脂质体—C—erbB2反义脱氧寡核苷酸对人卵癌裸鼠网膜移植瘤 …

目的 探讨脂质体－Ｃ－ｅｒｂＢ２反义脱氧寡苷酸（Ｃ－ｅｒｂＢ２ Ｓ－ＯＤＮｓ２）对人卵巢癌裸鼠网膜移植瘤生长及顺铂（ＤＤＰ）敏感性的影响。方法 对２０只裸鼠建立人卵巢癌裸鼠网膜移植模型,分为对照组（腹腔注射无菌水）、观察组（腹腔注射脂质体－Ｃ－ｅｒｂＢ２ Ｓ－ＯＤＮｓ）、化疗组（腹腔注射无菌水及ＤＤＰ）、观察＋化疗组（腹腔注射脂质体－Ｃ－ｅｒｂＢ２ Ｓ－ＯＤＮｓ及ＤＤＰ）。治疗期间观测裸鼠体重变化     

Type IV collagen and CD44v6 expression in benign, malignant primary and metastatic ovarian tumors: correlation with Ki-67 and p53 immunoreactivity

OBJECTIVE: Loss of basement membrane (BM) components, such as type IV collagen has been demonstrated in ovarian cancer, but the associations with other molecules like CD44v6, involved in metastatic process of ovarian carcinoma, have not been fully analyzed. This study investigates the expression of type IV collagen, CD44v6 molecule in correlation with p53 and Ki-67 presence in primary and metastatic lesion of ovarian carcinoma to define their role in metastases of ovarian carcinoma. METHODS: The expression of type IV collagen, CD44v6, p53, and Ki-67 was evaluated on frozen tissue sections from primary ovarian tumors (malignant n = 37, benign n = 16), metastatic lesions (n = 29) and ascitic fluid cells (n = 28). Protein expression of all studied biomarkers was evaluated in a subset of specimens using immunohistochemistry (IHC). RESULTS: Type IV collagen expression in the primary ovarian carcinoma was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor grade. Significant difference was observed for type IV collagen immunoreactivity in carcinoma cells in effusions when compared to corresponding primary tumors (P < 0.001) and metastatic lesions (P < 0.001). Likewise down-regulation of type IV collagen expression was seen in primary ovarian carcinomas (P = 0.01), ascitic fluid cells (P < 0.001), and metastases (P = 0.003) when compared to benign ovarian neoplasms. CD44v6 expression was detected in a comparable percentage of primary carcinomas (51%) and metastatic lesions (52%). In cells isolated from ascitic fluid, CD44v6 immunopositivity was observed in 43% of cases. A comparative analysis of primary and metastatic tumors and carcinoma cells in effusion did not reveal differences in expression of CD44v6. Positivity of CD44v6 was found in 2/16 (12%) of benign ovarian neoplasms. There were no significant differences between CD44v6 expression in benign neoplasms compared to primary malignant tumors and metastases (P > 0.05). CD44v6 expression in primary ovarian carcinomas was associated with higher tumor grade (P = 0.01) and histological type of tumors (P = 0.01). An inverse relationship of type IV collagen expression with p53 and CD44v6 positivity in benign and malignant ovarian tumors was found (P > 0.01). Type IV collagen expression was inversely correlated with p53 status (P = 0.03) in metastatic lesions. A slight trend toward an inverse correlation between Ki-67 and type IV collagen expression was observed in both benign and malignant ovarian tumors and metastases. CONCLUSIONS: Our data suggest that observed inverse correlation of type IV collagen expression with p53, CD44v6, and slight with Ki-67 positivity in primary benign and malignant tumors indicates that these molecules may cooperate in the invasion and progression of ovarian carcinomas.     

Comparison of p53, Ki-67, and CD44v6 expression between primary and matched metastatic lesions in ovarian cancer

OBJECTIVE: Many studies have demonstrated that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration causes tumor progression which plays a role in metastasis. Therefore, it could be expected that malignant potential in the metastatic site is more aggressive than that in the primary site. Using several immunohistochemical markers (p53, Ki-67, and CD44v6), we investigated an alteration of malignant potential. METHODS: We immunohistochemically examined expression of p53, Ki-67, and CD44 in primary and metastatic lesions of ovarian cancer. Fifty-six samples of primary lesions and matched metastatic sites from 56 patients with primary epithelial ovarian cancers were included in this study. RESULTS: In 16 cases (28%), the histological grade of the metastatic lesion increased. This difference was statistically significant (P = 0.0232). In 16 cases (28%), the expression of p53 increased in the metastatic lesions, in 5 pairs from negative to positive, whereas the case decrease in the metastatic lesions was only 1. This difference was statistically significant (P = 0.0046). There was no significant difference in Ki-67 labeling indices and expression of CD44v6 between the primary and matched metastatic lesions. The degree of p53 expression in the metastatic lesions significantly correlated with disease-free survival (P = 0.0482), whereas that in the primary lesions did not. Moreover, high p53 expression in the metastatic lesions significantly correlated with disease-free survival in multivariate analysis. CONCLUSIONS: The p53 expression in metastatic lesions may reflect an aggressive biologic behavior in ovarian cancer.     

钙黏素6基因在卵巢肿瘤组织中的表达及突变的研究

目的　通过研究卵巢肿瘤组织中钙黏素 (cadherin) 6基因的表达、突变及其临床意义 ,以寻找与卵巢肿瘤发生相关的分子水平标志物。方法　应用RT PCR技术和PCR 单链构象多态性方法分别检测恶性卵巢肿瘤组织 (4 1份 )、良性卵巢肿瘤组织 (15份 )、正常卵巢组织 (17份 )中cadherin 6mRNA的表达及cadherin 6基因的突变情况 ,并分析其临床意义。结果　正常卵巢组织、良性卵巢肿瘤组织、恶性卵巢肿瘤组织中cadherin 6mRNA阳性率分别为 71%、5 3%、2 4 % ,前两者显著高于后者 (P<0 0 5 )。cadherin 6mRNA阳性率与恶性卵巢肿瘤手术病理分期有关 ,Ⅲ～Ⅳ期恶性卵巢肿瘤组织中 ,cadherin 6mRNA阳性率 (5 % )显著低于Ⅰ～Ⅱ期 (4 5 % ,P <0 0 1)。 4 1例恶性卵巢肿瘤患者中 ,2例出现cadherin 6基因突变 ,而在正常卵巢组织和良性卵巢肿瘤组织中无cadherin 6基因突变。结论　cadherin 6mRNA在晚期恶性卵巢肿瘤组织中表达缺失。提示cadherin 6mRNA表达可作为判断恶性卵巢肿瘤预后的一个指标     

脆性组胺酸三聚体蛋白在上皮性卵巢肿瘤中的表达

目的 :探讨脆性组胺酸三聚体 (FHIT)蛋白在上皮性卵巢肿瘤组织中的表达及其意义 ,分析FHIT与P5 3蛋白、nm2 3 H1产物表达之间的相关性。方法 :应用免疫组化二步法检测 83例上皮性卵巢肿瘤蜡块组织标本中FHIT蛋白、P5 3蛋白及nm2 3 H1产物的表达。结果 :FHIT蛋白缺失仅见于恶性上皮性卵巢肿瘤 ,缺失率为 17.0 %。在良性与交界性上皮性卵巢肿瘤中未见FHIT蛋白缺失。在上皮性卵巢癌不同组织学分级中FHIT蛋白的缺失率分别为G10 / 6、G2 8.0 %、G331.8% ,低分化肿瘤FHIT蛋白缺失率显著高于高中分化肿瘤 (P <0 .0 5 ) ;在不同组织学类型中 ,FHIT蛋白缺失仅见于浆液性癌和透明细胞癌 ,缺失率分别为 2 5 .0 %和 1/ 3,在粘液性癌和子宫内膜样癌中未见FHIT蛋白缺失 ,但差异无显著性 (P >0 .0 5 ) ;FHIT蛋白缺失与淋巴结转移、残留癌灶大小及nm2 3 H1产物表达有明显相关性 ,与FIGO分期、有无腹水及P5 3蛋白表达无明显相关性。结论 :FHIT蛋白缺失是恶性上皮性卵巢肿瘤的特征 ,FHIT蛋白表达缺失在卵巢肿瘤的发生发展过程中有一定的作用 ,可能与上皮性卵巢癌的恶性进展及转移有关     

Heparanase expression correlates with poor survival in metastatic ovarian carcinoma

OBJECTIVE: To analyze the expression of Heparanase, an enzyme involved in cancer metastasis and angiogenesis, in ovarian and breast carcinoma cells in effusions. METHODS: Heparanase protein expression was analyzed in malignant effusions from ovarian (=200) and breast (=41) carcinoma patients using immunocytochemistry. The levels of secreted heparanase were analyzed in 45 effusion supernatants using a newly established ELISA test. Heparanase expression levels were analyzed for clinical significance. RESULTS: Heparanase was expressed at the cell membrane in 106/200 (53%) ovarian and 22/41 (54%) breast carcinomas. Cytoplasmic expression was found in 180/200 (90%) ovarian and 26/41 (63%) breast carcinomas. Reactive mesothelial cells showed frequent cytoplasmic, but not membrane expression. ELISA showed secreted heparanase in all 45 analyzed effusions. Higher levels were detected in peritoneal compared to pleural effusions (p=0.031). In univariate survival analysis of ovarian carcinoma patients with post-chemotherapy effusions, membrane expression in >5% of tumor cells correlated with shorter overall survival (OS, p=0.013). FIGO stage (p=0.03 for all patients, p=0.045 for those with post-chemotherapy specimens) and response to first-line chemotherapy (p<0.0001 for all patients, p=0.049 for those with post-chemotherapy specimens) were the clinical parameters related to OS. In Cox analysis of this subset of patients, heparanase expression (p=0.02) and response to chemotherapy (p=0.049) were independent predictors of poor OS. Heparanase expression did not correlate with survival in breast carcinoma. CONCLUSIONS: Our data show that heparanase is frequently expressed in metastatic gynecologic adenocarcinomas, and that it is secreted into the effusion fluid in body cavities. The correlation between heparanase expression and poor survival in ovarian carcinoma suggests a role for this molecule in ovarian cancer metastasis and supports its role as a marker of aggressive clinical behavior at disease recurrence.     

Tumor suppressor gene, cell surface adhesion molecule, and multidrug resistance in Müllerian serous carcinomas: clinical divergence without immunophenotypic differences

OBJECTIVES: We hypothesize that differences in the expression of selected tumor suppressor genes, cell surface adhesion molecules, and multidrug resistance glycoproteins could account for some of the reported differences between uterine serous carcinoma (USC) and extrauterine serous carcinomas (ESC), including ovarian and primary peritoneal carcinoma (OSC and PSC, respectively). METHODS: We studied the expression of the following antigens in 20 USCs, 20 OSCs, and 10 PSCs: p53 and mdm-2 (tumor suppressor genes), CD44 and CD44v6 (cell surface adhesion molecules), and the p-glycoprotein (a multidrug resistance protein recognized by two antibodies, C494 and JSB1). We further studied chemotherapeutic drug resistance by examining reports prepared using the Oncotech Extreme Drug Resistance Assay from 24 of the 50 study patients. Clinical data were obtained from medical record review. RESULTS: USC, OSC, and PSC patients were similar with respect to mean age at diagnosis, mean gravidity, mean parity, personal history of breast cancer, percentage treated with chemotherapy, and survival at 3 and 5 years postdiagnosis. Significant clinical differences included a high prevalence of nulliparity in OSC (P = 0.05), a low prevalence of Caucasian race in USC (P = 0.008), a paucity of stage I patients in OSC and PSC (P = 0.03), a high prevalence of familial breast cancer in OSC (P = 0.06), and superior 2-year survival in OSC (P = 0.02). Seventy-five percent of USCs, 52% of OSCs, and 60% of PSCs expressed p53. Five percent of USCs, 19% of OSCs, and 0% of PSCs expressed mdm-2. Forty percent of USCs, 33% of OSCs, and 10% of PSCs expressed CD44. None of the USCs, OSCs, or PSCs expressed CD44v6. Sixty-one percent of USCs and OSCs and 82% of PSCs expressed C494 while 17% of USCs, 19% of OSCs, and 20% of PSCs expressed JSB1. None of these apparent differences was statistically significant. USC, OSC, and PSCs patients did not demonstrate significant differences with respect to extreme drug resistance. However, the following trends were noted (P = 0.06): more prevalent low drug resistance for cyclophosphamide in OSC compared with USC and more prevalent extreme drug resistance for etoposide in OSC compared with USC. CONCLUSIONS: Therefore, despite significant clincial differences, the USCs and ESCs in our series do not differ significantly with respect to the expression of the tumor suppressor genes, cell surface adhesion molecules, and drug resistance proteins studied. It is premature, however, to recommend that USCs and ESCs should be treated identically.     

Clear cell carcinoma of the ovary: characterization of its CD44 isoform repertoire

OBJECTIVE: CD44 is a cell surface receptor implicated in tumor metastases. We have previously shown that there is a loss of CD44 splice control in clear cell carcinoma (CCCa) of the ovary. Our aim is to characterize the expression of CD44-3v, -5v, -7v, and -10v in clear cell ovarian tumors and to determine their prognostic value. METHODS: Twenty-two cases of ovarian CCCa were studied for CD44-3v, -5v, -7v, and -10v expression by immunocytochemistry. RESULTS: The primary tumors showed expression of CD44-3v, -5v, -7v, and -10v in 44, 55, 61, and 39% of the cases, respectively. We were able to compare the expression of CD44 in the primary tumor and metastatic sites from the same patient in 7 cases (metastatic sites n = 16). We observed decreased immunoreactivity of CD44-3v, -5v, -7v, and -10v in 67, 100, 93, and 92% of the sites, respectively. CD44-3v and -10v expression was absent in 100% of the nonaffected contralateral ovaries while -7v and -10v were expressed in 1/11 (9%) of them. When CD44-10v was not expressed in the primary tumor, only 18% of the women recurred or died of disease; in contrast, of the cases where it was present, 71% of the women recurred or died of disease (P = 0.049). CONCLUSIONS: There is aberrant alternative mRNA splicing in the development of CCCa of the ovary when compared to the contralateral nonaffected ovary. The expression of CD44-10v correlates with survival. Larger series are needed to further understand the role of CD44 isoforms in ovarian cancer metastases.     

CD44v6 expression is an independent prognostic factor in node-negative FIGO stage IB cervical carcinoma

Adhesion molecules such as CD44 play an important role in the metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. As a so-called "lymphocyte homing receptor," CD44 is physiologically involved in migration of circulating lymphocytes to lymphatic tissue. In the present study, we investigated the expression of CD44v3 and v6 in 237 patients with stage IB, N0 cervical carcinoma by means of immunohistochemistry. These results were correlated with the GOG score and other prognostic variables. Median follow-up was 82.6 months (39–110 months). Thirty-nine patients recurred and 35 died from disease within the observation period. In univariate analysis, the GOG score, histologic subtype, and CD44v6 expression were statistically significant predictors for poor overall survival (OS). In multivariate (Cox regression) analysis, the GOG score (< 40 vs. 40–120, RR: 1.37 (95% CI: 1.10–1.71); 40–120 vs. > 120, RR: 2.23 (95% CI: 1.28–3.88); P = 0.004), histologic subtype (adenosquamous carcinomas) (RR: 4.56 (95% CI: 1.49–13.92), P = 0.007) and CD44v6 expression (RR: 2.42 (95% CI: 1.14–5.10), P = 0.021) were independent predictors for poor OS. The expression of CD44v3 did not correlate with prognosis. Furthermore we found a strong correlation between CD44v6 expression and lymphovascular space invasion (LVSI) (χ² = 17.01, P = 0.0001). Tumor expansion into the loco-regional lymphatic system is the preferred way of tumor spread in cervical carcinoma. The strong correlation of CD44v6 with LVSI produces a significant degree of suspicion that cervical carcinoma cells expressing CD44v6 could, by mimicking lymphocytes, exploit their pathways.     

Correlation of CD44v5 expression with invasiveness and prognosis in renal cell carcinoma.

BACKGROUND AND PURPOSE: The expression of specific CD44 isoforms is associated with metastasis and poor prognosis in human malignant tumors. We retrospectively investigated the expression of the CD44 variant isoform v5 (CD44v5) in human renal cell carcinoma (RCC) specimens by immunohistochemistry. METHODS: We studied the expression of CD44v5 immunohistochemistry in archival tissue specimens from 72 RCC patients (47 men and 25 women) with a mean age of 60.1 years (range, 30 to 83 years) who underwent resection in our hospital from 1986 to 1996. The patients were divided into non-invasive (pT1, pT2, and pT3a; n = 49) and invasive groups (pT3b, pT3c, and any T with N+; n = 23). Among the 72 patients, 67 were followed for at least 60 months (up to 190 months) after radical nephrectomy. Twenty nine renal specimens, including 15 of normal renal parenchyma and 14 of inflammatory or immune renal diseases, were used as controls. RESULTS: All control group tissues expressed CD44v5. CD44v5 expression was detected in 66 of 72 RCC specimens (91.7%). In general, the expression of CD44v5 was higher in the non-invasive group [47/49 (95.9%) vs 19/23 (82.6%), p < 0.05]. Five cases were lost to follow-up. Thirty three of 67 patients (49.3%) died of RCC-related causes during the follow-up period. The CD44v5 non-expression group had a higher mortality rate than the expression group [4/5 (80%) vs 29/62 (46.8%), p < 0.001]. The 5-year and 10-year survival rates were significantly higher in patients with CD44v5 expression than in those without (p < 0.001). CONCLUSIONS: This study found that CD44v5 expression was greater in early stage than in advanced stage RCC and was associated with tumor progression and long-term survival. Although the survival analysis showed both tumor stage and CD44v5 expression were significant prognostic factors in RCC, only tumor stage remained an independent factor.