Please use this identifier to cite or link to this item:
|Title:||Clinical validation of a customized multiple signature microarray for breast cancer|
|Citation:||Tan, B.K.T., Tan, L.K., Yu, K., Puay, H.T., Lee, M., Lang, H.S., Chow, Y.W., Gay, H.H., Yeo, A.W.Y., Chow, P.K.H., Heng, N.K., Wei, S.Y., Lim, D.T.H., Ooi, L.L.P.J., Khee, C.S., Tan, P. (2008-01-15). Clinical validation of a customized multiple signature microarray for breast cancer. Clinical Cancer Research 14 (2) : 461-469. ScholarBank@NUS Repository. https://doi.org/10.1158/1078-0432.CCR-07-0999|
|Abstract:||Purpose: Current histopathologic systems for classifying breast tumors require evaluation of multiple variables and are often associated with significant interobserver variability. Recent studies suggest that gene expression profiles may represent a promising alternative for clinical cancer classification. Here, we investigated the use of a customized microarray as a potential tool for clinical practice. Experimental Design: We fabricated custom 188-gene microarrays containing expression signatures for three breast cancer molecular subtypes [luminal/estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2), and "basaloid"], the Nottingham prognostic index (NPI-ES), and low histologic grade (TuM1). The reliability of these multiple-signature arrays (MSA) was tested in a prospective cohort of 165 patients with primary breast cancer. Results: The MSA-ER signature exhibited a high concordance of 90% with ER immunohistochemistry reported on diagnosis (P < 0.001). This remained unchanged at 89% (P < 0.001) when the immunohistochemistry was repeated using current laboratory standards. Expression of the HER2 signature showed a good correlation of 76% with HER2 fluorescence in situ hybridization (FISH; ratio ≥2.2; P < 0.001), which further improved to 89% when the ratio cutoff was raised to ≥5. A proportion of low-level FISH-amplified samples (ratio, 2.2-5) behaved comparably to FISH-negative samples by HER2 signature expression, HER2 quantitative reverse transcription-PCR, and HER2 immunohistochemistry. Luminal/ER+ tumors with high NPI-ES expression were associated with high NPI scores (P = 0.001), and luminal/ER+ TuM1-expressing tumors were significantly correlated with low histologic grade (P = 0.002) and improved survival outcome in an interim analysis (hazard ratio, 0.2; P = 0.019). Conclusion: The consistency of the MSA platform in an independent patient population suggests that custom microarrays could potentially function as an adjunct to standard immunohistochemistry and FISH in clinical practice. © 2008 American Association for Cancer Research.|
|Source Title:||Clinical Cancer Research|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Nov 13, 2018
WEB OF SCIENCETM
checked on Nov 13, 2018
checked on Oct 26, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.