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.
Department of Gynecology, University Hospital Groningen, Groningen, The Netherlands.
G B
GB
Wisman
A J
AJ
Knol
M N
MN
Helder
M
M
Krans
E G
EG
de Vries
H
H
Hollema
S
S
de Jong
A G
AG
van der Zee
D002584:Cervix Uteri / Q000201:enzymology; D015331:Cohort Studies; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008207:Lymphatic Metastasis; D011379:Prognosis; D012313:RNA; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000096:biosynthesis*; D016896:Treatment Outcome; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000401:mortality* / Q000628:therapy
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase