Gene Expression Analysis and the Advantages of Fresh Tissue      


The presence of estrogen receptor (ER), progesterone receptor (PR) and HER2 assessed by immunohistochemistry (IHC) are strong predictive markers for response to endocrine (e.g. Tamoxifen) and trastuzamab-based (e.g. Herceptin®) therapies. It is known that differences in tissue fixation, choice of antibody, and interpretation can severely affect IHC accuracy and reproducibility.

A number of inter-laboratory comparison studies of hormone receptor status assessment and HER2 assessment have shown a considerable number of discrepant results (up to 30%). In development of TargetPrint, Agendia assessed the association between mRNA expression measured by microarray and IHC for ER, PR and HER2 in both local and central reference laboratories.(1-12)

TargetPrint uses mRNA-based receptor determination which has been shown to be a robust and reproducible method.  Moreover, mRNA expression measurements are performed over a broad dynamic range and thus provide true quantitative data.(13-15) 

References
  1. Hede K. Breast cancer testing scandal shines spotlight on black box of clinincal laboratory testing. J Natl Cancer Inst 2008;100:836-7.
  2. Oyama T, Ishikawa Y, Hayashi M, Arihiro K, Horiguchi J. The effects of fixation, processing and evaluation criteria on immunohistochemical detection of hormone receptors in breast cancer. Breast Cancer 2007;14:182-8.
  3. Ross JS, Symmans WF, Pusztai L, Hortobagyi GN. Standardizing slide-based assays in breast cancer: hormone receptors, HER2, and sentinel lymph nodes. Clin Cancer Res 2007;13:2831-5.
  4. Kirkegaard T, Edwards J, Tovey S, et al. Observer variation in immunohistochemical analysis of protein expression, time for a change? Histopathology 2006;48:787-94.
  5. Diaz LK, Sahin A, Sneige N. Interobserver agreement for estrogen receptor immunohistochemical analysis in breast cancer: a comparison of manual and computer-assisted scoring methods. Ann Diagn Pathol 2004;8:23-7.
  6. Arihiro K, Umemura S, Kurosumi M, et al. Comparison of evaluations for hormone receptors in breast carcinoma using two manual and three automated immunohistochemical assays. Am J Clin Pathol 2007;127:356-65.
  7. Gancberg D, Järvinen T, di Leo A, et al. Evaluation of HER-2/NEU protein expression in breast cancer by immunohistochemistry: an interlaboratory study assessing the reproducibility of HER-2/NEU testing. Breast Cancer Res Treat 2002;74:113-20.
  8. Allred DC. Commentary: hormone receptor testing in breast cancer: a distress signal from Canada. Oncologist 2008;13:1134-6.
  9. Viale G, Regan MM, Maiorano E, et al. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol 2007;25:3846-52.
  10. Rhodes A, Jasani B, Barnes DM, Bobrow LG, Miller KD. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol 2000;53:125-30.
  11. Perez EA, Suman VJ, Davidson NE, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 2006;24:3032-8.
  12. Reddy JC, Reimann JD, Anderson SM, Klein PM. Concordance between central and local laboratory HER2 testing from a community-based clinical study. Clin Breast Cancer 2006;7:153-7.
  13. Ach et al., 2007, Robust inter-laboratory reproducibility of a gene-expression signature measurement consistent with the needs of a new generation of diagnostic tools. BMC Genomics 8; 148
  14. Glas et al., 2006, Converting a breast cancer microarray signature into a high-throughput diagnostic test, BMC Genomics, 7:278
  15. Roepman et al., 2008, Microarray based read-out of ER, PR and HER2 expression in breast cancer tissue, abstract, abstract ASCO Breast Conference 2008
  16. Bueno-de-Mesquita et al, 2007, Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER), Lancet Oncology, 2007 Dec;8(12):1079-87
  17. van de Vijver et al, 2002, A gene-expression signature as a predictor of survival in breast cancer, New England Journal of Medicine, Dec 19;347(25)
  18. EBCTCG, Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365;1687-1717
  19. Ross et al. (2003) The Her-2/neu gene and protein in breast cancer: biomarker and target of therapy. Oncologist 8 (4): 307-25
 

RNA Integrity
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