Telomerase as a prognostic marker in breast cancer: high‐throughput tissue microarray analysis of hTERT and hTR

Poremba, Christopher; Heine, Bernhard; Diallo, Raihanatou; Heinecke, Achim; Wai, Daniel; Schaefer, Karl‐Ludwig; Braun, Yvonne; Schuck, Andreas; Lanvers, Claudia; Bànkfalvi, Àgnes; Kneif, Sören; Torhorst, J.; Zuber, Markus; Köchli, Ossi R.; Mross, F; Dieterich, H.; Sauter, Guido; Stein, Harald; Fogt, Franz; Boecker, Werner

doi:10.1002/path.1191

Cited by 112 publications

(71 citation statements)

References 40 publications

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“…2,[7][8][9][10][11][12][13] Even though a few studies have used tissue microarray to analyze ovarian carcinoma, 14,15 uncertainty has remained as to whether this technique is useful in such heterogeneous tumors. 16,17 Most validation studies have found that analysis of three 0.6-mm cores produces higher concordance rates than use of one core and that use of three cores also reduces the problems of higher case loss that is seen with two cores.…”

Section: Discussionmentioning

confidence: 99%

Validation of tissue microarray technology in ovarian carcinoma

et al. 2004

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High-throughput tissue microarray allows many clinical specimens to be analyzed simultaneously on a single slide. One potential limitation of tissue microarray is the correct representation of each tumor with the small tissue core. Because tumors from different organs have different levels of heterogeneity, it requires a validation study for each one of them. We compared immunostaining of Ki-67, estrogen receptors, and p53 in whole sections of 45 cases of high-grade serous ovarian carcinoma with six core samples from those sections with regard to the number of tissue cores needed to reliably represent a whole section. Staining for Ki-67 was graded high or low by automated image analysis of 10 high-power fields; staining for estrogen receptor and p53 was scored on a 0-to-3 scale. Correlation coefficients for whole-section vs core stains were 0.86 for Ki-67, 0.93 for estrogen receptors, and 0.82 for p53. A total of 54 (6.6%) of the cores were inadequate for scoring. The probability that results from one core would correctly represent all three markers in the whole section was 91%; that for two cores was 96%; and that for three cores was 98%. Our results show that analysis of a single readable core matched the staining pattern of a whole section more than 90% of the time, and analysis of two cores increased that value to more than 95%, demonstrating that ovarian carcinoma tissue microarray is a reliable technique to analyze the expression of markers.

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Section: Discussionmentioning

confidence: 99%

Validation of tissue microarray technology in ovarian carcinoma

et al. 2004

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“…Numerous studies have used TMA to validate promising results from diagnostic and prognostic biomarker discovery studies. Examples of validation of prognostic biomarkers include an association of elevated expression of COX2 [28], telomerase [29], Ep-CAM/TACSTD1 [30], and EPIL [31] with unfavorable outcome. Proteins associated with a favorable clinical outcome include PHLDA1 [32], and BCL2 [33].…”

Section: Proteomic Profiling Of Human Tissues and Fluidsmentioning

confidence: 99%

Breast tumor metastasis: analysis via proteomic profiling

Goodison¹,

Urquidi²

2008

Expert Review of Proteomics

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The ability to predict the metastatic behavior of a patient's cancer, as well as to detect and eradicate such recurrences, remain major clinical challenges in oncology. While many potential molecular biomarkers have been identified and tested previously, none have greatly improved the accuracy of specimen evaluation over routine histopathological criteria and, to date, they predict individual outcomes poorly. The ongoing development of high-throughput proteomic profiling technologies is opening new avenues for the investigation of cancer and, through application in tissue-based studies and animal models, will facilitate the identification of molecular signatures that are associated with breast tumor cell phenotype. The appropriate use of these approaches has the potential to provide efficient biomarkers, and to improve our knowledge of tumor biology. This, in turn, will enable the development of targeted therapeutics aimed at ameliorating the lethal dissemination of breast cancer. In this review, we focus on the accumulating proteomic signatures of breast tumor progression, particularly those that correlate with the occurrence of distant metastases, and discuss some of the expected future developments in the field.

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“…This prompted us in the present study to subject the same frozen tissues in which we had demonstrated telomerase activity by PCR-ELISA [TRAP-protocol, Kim et al (16)] to an immunohistochemical investigation to find out specifically which cells express the catalytic protein subunit of telomerase, human telomerase reverse transcriptase (hTERT). When we started, the only immunohistochemical hTERT results which had been published related to paraffin sections or cells embedded in paraffin (17)(18)(19)(20)(21)(22). The first challenge was therefore to determine which commercially available antibodies and which method would yield the best nuclear presentation of hTERT in frozen sections.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

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Abstract.In previous studies we demonstrated telomerase activity in frozen tissue from head and neck squamous cell carcinoma (HNSCC) and their tumor-free tumor margins. In the present study frozen sections from the same tissues were examined for in situ presence of hTERT. In preliminary investigations we established that the most suitable method of tissue preparation was fixation in acetone and methanol followed by steaming and visualization by APAAP. Most of the assays involved eleven anti-hTERT antibodies and were supplemented with the inclusion of antibodies Ki-67, antinucleolin and CD45. hTERT expression was investigated in the tissues of 61 patients with HNSCC and 37 patients without tumor. Semi-quantitative immunoreactive scores were correlated with telomerase activity. We examined the prognostic significance of hTERT expression with Kaplan-Meier curves and tested the immunological specificity of the antibodies by immunoabsorption with two hTERT peptides and a nucleolin peptide. Nuclear staining of satisfactory distribution and intensity was achieved in seven anti-hTERT antibodies both in the carcinomas and in the squamous epithelia of the tumor resection margins and in the control tissues. Proof of hTERT did not differ from telomerase activity. The telomerase activity demonstrated in tumor-free resection margins and in control tissues did, however, correlate with lymphocytic-monocytic infiltration (CD45 expression). This telomerase activity might be related to nuclear hTERT expression in the squamous epithelium, given that the hTERT score values in the connective tissue tended to be negative. The prognostic significance of hTERT expression demonstrated on paraffin sections from different tumor localizations was not confirmed for the frozen sections of patients with HNSCC. The hTERT specificity of the monoclonal NCL-L-hTERT, whose use as an antibody against hTERT has been questioned, was reexamined with immunohistochemical methods, but the intensity of its immunoabsorption with the nucleolin peptide did not exceed that observed in the other anti-hTERT antibodies.

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Telomerase as a prognostic marker in breast cancer: high‐throughput tissue microarray analysis of hTERT and hTR

Cited by 112 publications

References 40 publications

Validation of tissue microarray technology in ovarian carcinoma

Validation of tissue microarray technology in ovarian carcinoma

Breast tumor metastasis: analysis via proteomic profiling

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

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