Wisman G B, Knol A J, Helder M N, Krans M, de Vries E G, Hollema H, de Jong S, van der Zee A G
Department of Gynecology, University Hospital Groningen, Groningen, The Netherlands.
Int J Cancer. 2001 Mar 1;91(5):658-64. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1099>3.0.co;2-7.
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.
我们在宫颈癌中研究了端粒酶活性、端粒酶RNA（hTR）和端粒酶催化亚基的mRNA（hTERT）与“经典”临床病理因素以及生存率之间的关系。从107例连续的宫颈癌患者中获取冷冻标本，这些患者接受了手术或放疗，有的还接受了化疗。采用基于荧光的端粒重复序列扩增法（TRAP）测定端粒酶活性，采用半定量逆转录聚合酶链反应（RT-PCR）测定hTR和hTERT。8例正常宫颈标本作为对照。预后因素分析和生存率分析仅限于主要接受根治性子宫切除术的早期患者。正常宫颈中未检测到端粒酶活性，107例宫颈癌中有85例（79%）检测到端粒酶活性（p<0.001）。所有正常宫颈和宫颈癌中均检测到hTR，而8例正常宫颈中有1例（13%）、104例宫颈癌中有83例（80%）检测到hTERT mRNA（p<0.001）。与半定量hTR表达水平相反，半定量hTERT mRNA水平与端粒酶活性水平相关（p<0.01）。在所有患者中，端粒酶活性水平与分化程度相关（p<0.05），但与分期和组织类型无关。在早期患者中，端粒酶活性、hTR和hTERT与肿瘤体积、血管侵犯或转移性淋巴结的存在无关。肿瘤体积、血管侵犯和转移性淋巴结的存在与（无进展）生存率相关，而端粒酶活性及其亚基则无关。在宫颈癌中尤其观察到端粒酶活性和hTERT mRNA频繁上调，而在正常宫颈中也检测到hTR。端粒酶不适用于早期宫颈癌患者的预后评估。
