Telomerase in relation to clinicopathologic prognostic factors and survival in cervical cancer

We investigated, in cervical cancer, the relation between telomerase activity, telomerase RNA (hTR) and mRNA of the catalytic subunit of telomerase, hTERT, with "classic" clinicopathological factors as well as survival. Frozen specimens were obtained from 107 consecutive patients with cervical cancer, treated with surgery or radiotherapy with or without chemotherapy. Telomerase activity was determined with fluorescence-based TRAP and hTR and hTERT with semi-quantitative RT-PCR. Eight normal cervical specimens served as controls. Analysis of prognostic factors and survival was limited to early-stage patients, treated primarily with radical hysterectomy. Telomerase activity was not detected in normal cervices and was present in 85 of 107 (79%) cervical cancers (p < 0.001). hTR was detected in all normal cervices and cervical cancers, while hTERT mRNA was detected in 1 of 8 (13%) normal cervices and in 83 of 104 (80%) cervical cancers (p < 0.001). In contrast to semi-quantitative hTR expression levels, semi-quantitative hTERT mRNA levels were related to telomerase activity levels (p < 0.01). In all patients, telomerase activity levels were related to differentiation grade (p < 0.05) but not to stage and histotype. In early-stage patients, telomerase activity, hTR and hTERT were not related to tumor volume, vascular invasion or presence of metastatic lymph nodes. Tumor volume, vascular invasion and presence of metastatic lymph nodes were related to (progression-free) survival, while telomerase activity and its subunits were not. Frequent up-regulation of telomerase activity and hTERT mRNA is especially observed in cervical cancers, while hTR is also detected in normal cervices. Telomerase is not applicable as a prognostic factor in early-stage cervical cancer patients.     

端粒酶基因和抗凋亡基因bcl-2在肺组织中的表达研究

 目的　研究肺癌端粒酶基因和bcl 2的关系 ,以期阐明端粒酶基因及抗凋亡基因对端粒酶的调控机理。方法　采用TRAP、RT PCR及LSAB的方法研究了肺癌端粒酶活性、hTR、hTERT及bcl 2的表达。结果　 82 .3%的肺癌组织表达端粒酶阳性 ,38例癌组织中 ,34例表达hTR (89.4 % ) ,36例表达hTERT(94 .7% )。而在相应的癌旁组织中 ,34例表达hTR ,但只有 3例表达hTERT(7.8% )。结论　肺癌组织中具有较高的端粒酶活性 ,在肿瘤组织和正常组织中hTERT的表达有显著的差异 (P <0 .0 5 )。hTR在正常组织和肿瘤组织均有较高的表达 ,bcl 2的表达与端粒酶基因有着较高的相关性。     

Clinical utility of telomerase in cancer

This review will focus on the clinical utilities of telomerase for human cancer diagnosis. Much attention has been focused on detection of telomerase activity and its essential components (hTR and hTERT) in cancer and noncancerous tissues. Expression of hTR and hTERT is upregulated in almost all human malignant tumors but not in benign or normal tissues with the exception of germline cells, proliferative stem cells, activated lymphocytes, and certain benign tumors. Thus, telomerase is a useful marker for cancer diagnosis and in some instance as a prognostic indicator of outcome. Telomerase detection in cells derived from breast fine needle aspirates, bronchial washes, and pancreatic juices show high sensitivity and specificity for cancer detection. In tissue samples, the level of telomerase activity is a useful prognostic indicator in certain adult cancers such as gastric and colon cancers and in neuroblastomas. Immunohistochemical detection of hTERT will facilitate exact diagnosis of the telomerase positive cells and expand the application of telomerase in cancer diagnosis.     

Differential telomerase activity, expression of the telomerase catalytic sub-unit and telomerase-RNA in ovarian tumors.

Telomerase activity has been found in a variety of malignant tumors but only rarely in benign tumors or normal tissues. In this study, we investigated telomerase activation in 37 ovarian tumors, including benign, borderline and malignant neoplasms. Telomerase activity was detected using the telomeric repeat amplification protocol (TRAP) in 13/16 ovarian carcinomas, 9/10 borderline tumors and 3/11 cystadenomas/fibromas. mRNA expression of the putative human telomerase catalytic sub-unit gene (hTERT) was detected by RT-PCR in 14/15 ovarian carcinomas, 8/10 borderline tumors and 4/11 cystadenomas/fibromas. In situ hybridization was performed to evaluate telomerase-RNA (hTR) expression in the corresponding paraffin-embedded tumors. Variable expression levels of hTR were found over neoplastic tumor cells. The highest levels of hTR expression were found predominantly in ovarian carcinomas. Although the amount of telomerase activity varied, significantly high levels of telomerase activity were found predominantly in ovarian carcinomas. hTERT mRNA expression was closely associated with telomerase activity. These findings suggest that up-regulation of hTERT and hTR is important for telomerase activation during malignant-tumor progression. Telomerase activation might therefore be a valuable diagnostic parameter that could help to identify potentially progressive lesions. However, the diagnostic and therapeutic implications of telomerase activation need to be clarified in clinical trials. Int. J. Cancer (Pred. Oncol.) 84:426-431, 1999.