卵巢癌组织中Bmi-1蛋白的表达与端粒酶活性的关系

目的通过检测癌基因Bmi-1在卵巢上皮癌中表达情况,探讨其与端粒酶活性的关系。方法①使用Reahime—PCR的方法检测47例卵巢上皮癌组织中Bmi-1基因的mRNA表达情况;②采用免疫组化SP法检测47例卵巢上皮癌组织中Bmi-1蛋白的表达;③改良端粒重复序列扩增技术（telomerase repeat amplification protocol）——TRAP-银染技术检测该47例卵巢上皮癌组织中端粒酶基因水平;④Western Blot检测卵巢上皮癌组织中端粒酶蛋白表达量。结果①Bmi-1蛋白在卵巢上皮癌组织中较正常组织有明显表达（P〈0．05）,并且与病理分级和临床分期有关,G3级阳性表达率（93．10％）高于G2级（61．11％）,Ⅱ期、Ⅲ期阳性表达率（66．67％）低于Ⅳ期（92．31％）,二者均有统计学差异（P〈0．05）。②卵巢上皮癌组织中端粒酶活性阳性检测率为87．23％（41／47）,正常组织中阴性表达;③端粒酶活性阳性标本中Bmi-1蛋白高表达,占90．24％,spearman相关性分析显示Bmi-1蛋白表达与端粒酶活性阳性率呈正相关（P〈0．05）。结论Bmi-1基因和蛋白在卵巢上皮癌组织中高表达,其表达率与组织学分级和临床期别相关;Bmi-1阳性率与端粒酶活性阳性率密切相关,其在卵巢癌的发病过程中可能有重要意义．值得进一步研究。     

乳癌组织端粒酶活性表达及其与p16基因的关系

目的：探讨乳房恶性肿瘤组织中端粒酶活性的表达情况及ｐ１６抑癌基因的影响。方法：应用端粒重复放大程序－酶标法（ＴＲＡＰ－ＥＬＩＳＡ）及ＴＲＡＰ－银染法检测３５例有乳癌组织及２４例良性肿瘤组织中的端粒酶活性,并采用多重ＰＣＲ技术对乳癌组织的ｐ１６基因的缺失空谈进行了分析,结果：３５例乳癌标本中有２８例端粒酶活性表达为阳性（８０％）,而２４例乳房良性肿瘤标本中仅１例端粒酶活性表达阳性（４．１％）。此外３５例乳癌标本中的１５例存在有ｐ１６基因的外显子２及外显子１的缺失（４２．８％）,而该１５例中有１４例被检测为端粒酶活性阳性（９３．３％）,但２０例未缺失标本的端粒酶阳怀率仅为７０％（１４／２０）。结论：端粒酶活性与乳房肿瘤组织的恶性程度密切相关,提示端粒酶参与了肿瘤的形成过程,而端粒酶活性的增高与ｐ１６抑癌基因的缺失突     

端粒酶活性检测在妇科肿瘤早期诊断中的应用

目的　观察端粒酶活性在妇科肿瘤中的阳性率 ,探讨妇科肿瘤发生过程中端粒酶所起的作用及其在妇科肿瘤早期诊断及预后中的诊断价值。方法　用以PCR为基础的端粒重复序列扩增 (TRAP)法测定 83例妇科肿瘤标本及正常对照标本中的端粒酶活性　结果　在 6 2正常对照标本中发现 5例有端粒酶的活性表达 (8.1% ) ,在 83例子宫颈癌、卵巢癌、子宫内膜癌中端粒酶阳性率为 94 % ,和正常对照组比较 ,差异显著 (P <0 .0 0 1)。结论　端粒酶活化是妇科肿瘤中的普遍现象 ,检测端粒酶活性对早期诊断妇科肿瘤有一定意义。     

C-erbB-2基因表达与卵巢肿瘤的关系研究

目的研究卵巢肿瘤中C-erbB-2基因的表达,探讨C-erbB-2基因在卵巢肿瘤发生发展中的作用及作为一种肿瘤标记物用于临床筛查和判断预后的临床意义。方法应用免疫组织化学的方法检测20例正常卵巢组织、30例卵巢恶性肿瘤、20例卵巢良性肿瘤中C-erbB-2的基因表达情况。用卡方检验（Chi-Square Test）检测C-erbB-2在卵巢肿瘤组织中的表达。结果卵巢恶性肿瘤组织中C-erbB-2基因阳性表达率为73.3%,卵巢良性肿瘤组织为15%,正常卵巢组织中为0%,无C-erbB-2过表达。在临床分期中,Ⅰ～Ⅱ期卵巢癌C-erbB-2基因阳性表达率为33.3%,Ⅲ～Ⅳ期为90.5%。结论 1.在卵巢恶性肿瘤组织中C-erbB-2基因表达异常或扩增。2.C-erbB-2作为影响细胞凋亡因子,基因过表达与卵巢肿瘤的发生发展有关,其检测为判断卵巢肿瘤的预后提供重要的理论依据。     

星形细胞肿瘤中端粒酶与PTEN的表达及相关性

目的：研究星形细胞肿瘤中的端粒酶活性和PTEN表达,探讨其在星形细胞肿瘤发生发展过程中的相关性,方法：收集手术切除经病理证实的星形细胞肿瘤110例,8例正常脑组织作对照。用端粒酶原位杂交检测盒检测组织标本端粒酶活性,用LSAB法检测PTEN表达。结果：星形细胞肿瘤端粒酶活性和PTEN的阳性检出率分别为50％（55／110）和39．1％（43／110）,且随着肿瘤恶性程度的增加,端粒酶活性程度升高（P＜0．01）,端粒酶活性与PTEN表达有相关性（P＜0．01）,结论：端粒酶活性与星形细胞肿瘤的分化程度有关,提示端粒酶活性可能是星形细胞肿瘤恶性程度的重要标记物,PTEN蛋白可能对端粒酶的活性有调节作用。     

人非小细胞肺癌细胞中端粒酶活性的检测与研究

目的 研究非小细胞肺癌细胞癌组织中端粒酶活性表达,探讨端粒酶生表达与非小细胞肺癌发生发展的关系。方法 收集经手术及病理证实的非小细胞肺癌４８例标本,１２例肺癌癌旁肺组织、７例非肿瘤病例所取正常肺组织作对照。用端粒酶检测试剂盒检测组织本端粒酶活性。结果 ７５．００％（３６／４８）非小细胞肺癌组织标本检出端粒酶活性,８．３３％（１／１２）癌旁肺组织检出端粒酶活笥,７例非肿瘤标本所取的正常肺组织均未检出     

食管癌及癌旁组织中端粒酶活性检测及其意义

目的探讨食管癌及癌旁组织中端粒酶活性检测的意义. 方法采用 PCR技术为基础的 TRAP法检测了 39例食管癌及癌旁组织端粒酶活性. 结果 39例食管癌组织中 34例端粒酶活性阳性,阳性率为87.2%,癌旁组织中3例阳性,阳性率为7.7%,9例食管良性组织中1例阳性,阳性率为11.1%.食管癌与相应癌旁组织和良性食管组织端粒酶阳性检测率相比,差异有显著性意义(p<0. 01).伴有淋巴结转移的 25例食管癌端粒酶阳性检测率为96.0%,显著高于未伴有淋巴结转移的阳性率(71.4%),两者差异有显著性意义(p<0.05). 结论端粒酶激活与食管癌发生发展有关,对端粒酶活性进行检测对食管癌的诊断和判断预后有重要价值.     

端粒酶在宫颈癌及癌前病变活检标本中的表达及意义

目的：探讨端粒酶在宫颈活检组织中的表达及意义。方法：采用端粒重复序列扩增-酶标法（TRAP-ELISA）测定了33例宫颈活检标本中端粒酶活性,其中宫颈癌25例（包括2例原位癌）,宫颈不典型增生8例,结果：宫颈癌端粒酶阳性检出率为92.0%,不典型增生阳笥检出率为25.0%,结论：宫颈活检组织端粒酶检测,可用于宫颈癌的早期诊断;对有效粒酶活性表达的病例进行了监测,可能有助于揭示宫颈癌的发生发展过程,宫颈上皮癌变的预测。     

食管癌及癌旁组织中端粒酶活性检测及其意义

目的探讨食管癌及癌旁组织中端粒酶活性检测的意义.方法采用PCR技术为基础的TRAP法检测了39例食管癌及癌旁组织端粒酶活性.结果39例食管癌组织中34例端粒酶活性阳性,阳性率为87.2%,癌旁组织中3例阳性,阳性率为7.7%,9例食管良性组织中1例阳性,阳性率为11.1%.食管癌与相应癌旁组织和良性食管组织端粒酶阳性检测率相比,差异有显著性意义(p<0.01).伴有淋巴结转移的25例食管癌端粒酶阳性检测率为96.0%,显著高于未伴有淋巴结转移的阳性率(71.4%),两者差异有显著性意义(p<0.05).结论端粒酶激活与食管癌发生发展有关,对端粒酶活性进行检测对食管癌的诊断和判断预后有重要价值.     

p53蛋白表达及端粒酶活性与骨组织恶性肿瘤关系的研究

目的 探讨端粒酶活性表达及p53基因蛋白产物在骨组织恶性肿瘤发生、发展中的作用。方法 采用非放射性同位素TRAP-银染方法对37例骨组织恶性肿瘤及13例同一病人的肿瘤旁对照组织中端粒酶活性进行检测,p53蛋白表达的检测是运用微波处理的LSAB免疫组化法。结果 37例骨组织恶性肿瘤端粒酶活性检出率为83.8％(31/37);同时检测的13例同一病人的肿瘤旁对照组织均未检测到端粒酶活性;p53蛋白表达检测结果为51.3％(19/37),正常对照组织无1例阳性。其中p53蛋白表达阳性的19例中16例端粒酶活性有表达。结论 端粒酶活性表达可能是骨肿瘤恶性的一种潜在生化标志物,并且可能和p53基因一起参与骨肿瘤的发生、发展过程,并具有协同作用。     

Evaluation of telomerase activity in cutaneous melanocytic proliferations

Telomerase is an enzyme which synthesizes the telomeres, TTAGGG repeats at the end of vertebrate chromosomes. Its activity is suppressed in the majority of somatic cells, whereas it is detectable in most tumor cell lines and human cancers. Telomerase activity has been evaluated in many tumors for diagnostic purposes, and an increase thereof has been found with tumor progression. In our study we used anonisotopic polymerase chain reaction (PCR)-based TRAP (telomeric repeat amplification protocol) method to quantify the level of telomerase activity in a series of cutaneous melanocytic lesions. Thirty-three benign nevi, 8 dysplastic nevi, 38 malignant melanomas, and 4 melanoma metastases were analyzed. Mean relative telomerase activity was low in benign nevi (3.5+/-2.9), and significantly increased in dysplastic nevi (13.1+/-6.8), malignant melanomas (49.8+/-29.6), and metastases (121.2+/-11.2). In addition to the evaluation of telomerase activity as a possible diagnostic tool, its increase with tumor progression also suggest a prognostic role in cutaneous melanoma.     

端粒酶转录酶及其调节相关蛋白与增殖细胞核抗原在卵巢上皮性肿瘤中的表达及临床意义

目的　探讨端粒酶转录酶 (hTERT)及端粒酶调节相关蛋白 (TRAP)与增殖细胞核抗原(PCNA)在卵巢上皮性肿瘤中的表达和临床意义。方法　收集 10 6例卵巢上皮性肿瘤 (恶性 5 4例 ,交界性 33例 ,良性 19例 )的临床资料 ,行hTERT、TRAP和PCNA 3种抗体的免疫组织化学标记链霉素卵白素生物素 (LSAB)法染色。对 87例恶性和交界性患者进行了随访 ,4 5例获结果 ,随访时间为 2～6 0个月。结果　hTERT蛋白的表达在良性 (4/ 19)和交界性 (90 9% ,30 / 33)以及良性和恶性(94 4 % ,5 1/ 5 4 )间的差异均有显著性 (P均 <0 0 0 1) ,TRAP蛋白的表达在良性 (4/ 15 )和恶性(77 8% ,2 8/ 36 )间的差异有显著性 (P <0 0 0 1) ;hTERT和TRAP蛋白的表达在卵巢癌Ⅰ、Ⅱ期和Ⅲ、Ⅳ期两组病例中的差异均无显著性 (P >0 0 5 ,P >0 3)。PCNA的表达在良性 (6 9± 5 9) %和交界性 (2 6 4± 17 8) %、良性和恶性 (5 1 8± 2 2 1) %以及交界性和恶性间的差异均有显著性 (P <0 0 1,P <0 0 0 1,P <0 0 5 )。 33例交界性患者全部存活 ,5 4例恶性患者中 35例 (6 4 8% )有转移 (包括 5例淋巴结转移 ) ,4例 (7 4 % )死亡。结论　hTERT和TRAP蛋白的表达与卵巢上皮性肿瘤的良恶性有关 ,但与其临床分期无关 ;hTERT和TRAP蛋白的表达相似     

Prognostic implication of telomerase activity in patients with brain tumors

Telomerase adds telomeric repeats to the ends of telomeres to compensate for their progressive loss. A favorable prognosis is associated with low or no telomerase in some tumors. The authors investigated whether telomerase activity is associated with survival of patients with brain tumors. Sixty-two consecutive patients with brain tumors underwent surgery, and their surgical specimens were investigated. The patients were pathologically categorized as group I (aggressive group) and group II (non-aggressive group). Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay. The median time was calculated in association with overall survival and progression-free survival in each group. The significant difference was noted in telomerase activity between high-grade gliomas and lowgrade gliomas (p=0.022). Telomerase activity was significantly associated with the median overall survival and progression-free survival in all tumors of the aggressive group. On the other hand, the median overall survival in the non-aggressive group was not dependent on telomerase activity, while the median progression-free survival was. Our data suggests that telomerase is an important prognostic indicator of survival in patients with brain tumors.     

Telomerase activity in benign bone tumors and tumor-like lesions

To assess the role and status of telomerase activity in benign bone tumors and tumor-like lesions, we performed telomerase assays in four giant cell tumors of bone, four fibrous dysplasias, three osteochondromas, three aneurysmal bone cysts, two osteoblastomas, one juvenile bone cyst and one myositis ossificans. A very sensitive non-radioactive TRAP assay was applied. Low level activity was detected in 7 of 18 tumor samples (38.9%), and high level activity was not detected in any of the cases. Telomerase activity was observed in all patients with osteochondromas, in two of the three aneurysmal bone cysts, in one of the four giant cell tumors of bone and in one of the four fibrous dysplasias, but not in osteoblastomas, juvenile bone cyst and myositis ossificans. Although the origin of this enzyme is still unclear, it might play a role in precancerous immortalization of benign bone tumors. Other possible reasons explaining the occurrence of telomerase activity, such as migrating lymphocytes or contamination of immortalized non-tumor cells, should not be ruled out. Telomerase activity, however, does exist in those samples having no malignant phenotype, for which reason telomerase assays are not always useful for the clinical and diagnostic approach in benign bone tumors. Determination of the telomerase status in benign lesions may contribute to a better understanding of the regulation mechanism of telomerase activity during progression of bone tumors.     

Telomerase activity in well-differentiated papillary thyroid carcinoma corrrelates with advanced clinical stage of the disease

Clinical relevance and stage correlation of telomerase activity in well-differentiated papillary thyroid carcinoma (WD PTC) has not been well determined, as its reported activity could be due to the analysis of tumors with lymphocytic infiltrates or aggressive variants of papillary carcinomas. We conducted a prospective study of telomerase activity in WD PTC without inflammatory infiltrates and correlated it with clinical stage. Fifty WD PTCs were analyzed for telomerase activity by PCR-based TRAP (telomeric repeat amplification protocol) assay. Results were correlated with stage and other clinicopathologic variables. Twenty-one (42%) WD PTCs demonstrated telomerase activity. The enzyme was detected more frequently in stage III/IVa WD PTCs (p=0.02) and in tumors with extra thyroidal extension (p=0.04). The risk of presenting advanced disease (stage III/IVa) and extrathyridal growth was significantly increased in telomerase-positive tumors (p=0.01; odds ratio [OR] 4.4 [95%Cl 1.3–14.7]) and (p=0.04; OR 3.6 [95%Cl 1.1–11.7]), respectively. Also, a correlation was found between telomerase activity and age. There was no correlation of telomerase activity with gender, histologic variant, tumor size, or cervical lymph node metastasis. Telomerase activity was observed in 42% of WD PTC and was detected more frequently in AJCC TNM stage III/IVa cases. This finding suggests that telomerase deregulation could be involved in tumor progression.