hTERT mRNA expression is associated with a poor clinical outcome in human breast cancer.
BACKGROUND
Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal length and stability thus leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase) gene is the rate-limiting determinant of telomerase reactivation. The present study aims to quantitatively measure the expression of hTERT mRNA in human breast cancer, examine the association between hTERT and the clinicopathological characteristics of the cancer specimens including the Nottingham Prognostic Index (NPI) and to explore the relationship between hTERT expression and clinical outcome.


METHODS
RNA was extracted from 116 breast carcinomas and 31 matched adjacent non-cancerous tissue (ANCT). hTERT mRNA expression was estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology.


RESULTS
hTERT mRNA was present in all of the cancerous specimens (mean=0.1701, median=0.0205) and most ANCT specimens with levels being 2.6 times higher in the cancerous tissue than in ANCT (mean=0.156 vs. 0.68, p=0.18). The mean mRNA levels increased with NPI scores (0.0816 for NPI 1, 0.1186 for NPI 2 and 0.68 for NPI 3), however this failed to reach statistical significance (P-values= 0.33 for NPI 1 vs. 2, 0.27for NPI2 vs. 3 and 0.24 for NPI 1 vs. 3). hTERT levels also increased with increasing tumour's grade (mean= 0.0459 for grade 1, 0.111for grade 2, and 0.27 for grade 3) but this trend did not reach a statistical significance. Low levels of hTERT were associated with mucinous carcinoma compared with ductal (p=0.023) and lobular (p=0.021) types. hTERT mRNA levels were higher in patients who had recurrent disease or died from breast cancer compared with those who remained alive without disease after a median follow up of 6 years (p=0.0026).


CONCLUSIONS
High hTERT mRNA levels are associated with a poor clinical outcome in human breast cancer and should be included as a prognostic marker in future validation studies.
Elkak
A
A
St. George's, University of London, UK.
Mokbel
R
R
Wilson
C
C
Jiang
W G
WG
Newbold
R F
RF
Mokbel
K
K
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D006801:Humans; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*; D016896:Treatment Outcome
D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase