title: Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR.
abstract: Telomerase activity (TA) has been shown to correlate with poor clinical outcome in various tumour entities, indicating that tumours expressing this enzyme may be more aggressive and that TA may be a useful prognostic marker. For breast cancer, however, TA is a controversial prognostic marker; whereas some studies suggest an association between TA and disease outcome, others do not find this association. This study used tissue microarrays (breast carcinoma prognosis arrays) containing 611 samples (each 0.6 mm in diameter) from the tumour centre of paraffin-embedded breast carcinomas to analyse the catalytic subunit of telomerase, human telomerase reverse-transcriptase (hTERT), and the internal RNA component (hTR), which are the core components of the telomerase holoenzyme complex. hTERT protein expression was obtained by immunohistochemistry (human anti-telomerase antibody Ab-2, Calbiochem), and hTR RNA was measured by radioactive in situ hybridization. hTERT and hTR expression were determined semi-quantitatively and graded (scores 1-4). Clinical data, such as histological subtype, pT stage, tumour diameter, pN stage, BRE grade, tumour-specific survival (in months), patient's age and others, were available for statistical analysis. A statistically significant correlation was found between tumour-specific survival (overall survival) and hTERT expression (p < 0.0001) or hTR expression (p = 0.00110). Tumours with higher scores (scores 3, 4) for hTR and/or hTERT were associated with a worse prognosis. In multivariate analysis, hTERT expression was an independent prognostic factor. Previous studies, focusing on analysis of TA in smaller numbers of fresh-frozen breast carcinomas by the TRAP assay, gave controversial results with respect to TA as a prognostic marker. Using tissue microarrays from 611 breast carcinomas, this study has demonstrated that increased expression levels of the telomerase core components, hTERT and hTR, are associated with lower overall survival. These findings suggest that TA should be included in future validation studies as a prognostic marker in breast cancer.
authors.affiliation: Gerhard-Domagk-Institute of Pathology, Westfälische Wilhelms-University, Domagkstrasse 17, 48149 Münster, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
authors.forename: Bernhard
authors.initials: B
authors.lastname: Heine
authors.forename: Raihanatou
authors.initials: R
authors.lastname: Diallo
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Daniel
authors.initials: D
authors.lastname: Wai
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Schaefer
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Braun
authors.forename: Andreas
authors.initials: A
authors.lastname: Schuck
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanvers
authors.forename: Agnes
authors.initials: A
authors.lastname: Bànkfalvi
authors.forename: Sören
authors.initials: S
authors.lastname: Kneif
authors.forename: Joachim
authors.initials: J
authors.lastname: Torhorst
authors.forename: Markus
authors.initials: M
authors.lastname: Zuber
authors.forename: Ossi R
authors.initials: OR
authors.lastname: Köchli
authors.forename: Frank
authors.initials: F
authors.lastname: Mross
authors.forename: Holger
authors.initials: H
authors.lastname: Dieterich
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Franz
authors.initials: F
authors.lastname: Fogt
authors.forename: Werner
authors.initials: W
authors.lastname: Boecker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D012313:RNA / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D015996:Survival Rate; D019098:Telomerase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase