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Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR.
J Pathol. 2002 Oct; 198(2):181-9.JP

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+Show Affiliations

Gerhard-Domagk-Institute of Pathology, Westfälische Wilhelms-University, Domagkstrasse 17, 48149 Münster, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12237877

Citation

Poremba, Christopher, et al. "Telomerase as a Prognostic Marker in Breast Cancer: High-throughput Tissue Microarray Analysis of hTERT and HTR." The Journal of Pathology, vol. 198, no. 2, 2002, pp. 181-9.
Poremba C, Heine B, Diallo R, et al. Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR. J Pathol. 2002;198(2):181-9.
Poremba, C., Heine, B., Diallo, R., Heinecke, A., Wai, D., Schaefer, K. L., Braun, Y., Schuck, A., Lanvers, C., Bànkfalvi, A., Kneif, S., Torhorst, J., Zuber, M., Köchli, O. R., Mross, F., Dieterich, H., Sauter, G., Stein, H., Fogt, F., & Boecker, W. (2002). Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR. The Journal of Pathology, 198(2), 181-9.
Poremba C, et al. Telomerase as a Prognostic Marker in Breast Cancer: High-throughput Tissue Microarray Analysis of hTERT and HTR. J Pathol. 2002;198(2):181-9. PubMed PMID: 12237877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR. AU - Poremba,Christopher, AU - Heine,Bernhard, AU - Diallo,Raihanatou, AU - Heinecke,Achim, AU - Wai,Daniel, AU - Schaefer,Karl-Ludwig, AU - Braun,Yvonne, AU - Schuck,Andreas, AU - Lanvers,Claudia, AU - Bànkfalvi,Agnes, AU - Kneif,Sören, AU - Torhorst,Joachim, AU - Zuber,Markus, AU - Köchli,Ossi R, AU - Mross,Frank, AU - Dieterich,Holger, AU - Sauter,Guido, AU - Stein,Harald, AU - Fogt,Franz, AU - Boecker,Werner, PY - 2002/9/19/pubmed PY - 2003/1/8/medline PY - 2002/9/19/entrez SP - 181 EP - 9 JF - The Journal of pathology JO - J Pathol VL - 198 IS - 2 N2 - 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. SN - 0022-3417 UR - https://www.unboundmedicine.com/medline/citation/12237877/Telomerase_as_a_prognostic_marker_in_breast_cancer:_high_throughput_tissue_microarray_analysis_of_hTERT_and_hTR_ L2 - https://doi.org/10.1002/path.1191 DB - PRIME DP - Unbound Medicine ER -