PMID- 18223220 OWN - NLM STAT- MEDLINE DCOM- 20080327 LR - 20191210 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 14 IP - 2 DP - 2008 Jan 15 TI - Clinical validation of a customized multiple signature microarray for breast cancer. PG - 461-9 LID - 10.1158/1078-0432.CCR-07-0999 [doi] AB - 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 > or =2.2; P < 0.001), which further improved to 89% when the ratio cutoff was raised to > or =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. FAU - Tan, Benita K T AU - Tan BK AD - Department of General Surgery, Singapore General Hospital, Singapore. FAU - Tan, Lay Keng AU - Tan LK FAU - Yu, Kun AU - Yu K FAU - Tan, Puay Hoon AU - Tan PH FAU - Lee, Ming AU - Lee M FAU - Sii, Lang Hiong AU - Sii LH FAU - Wong, Chow Yin AU - Wong CY FAU - Ho, Gay Hui AU - Ho GH FAU - Yeo, Allen W Y AU - Yeo AW FAU - Chow, Pierce K H AU - Chow PK FAU - Koong, Heng Nung AU - Koong HN FAU - Yong, Wei Sean AU - Yong WS FAU - Lim, Dennis T H AU - Lim DT FAU - Ooi, London L P J AU - Ooi LL FAU - Soo, Khee Chee AU - Soo KC FAU - Tan, Patrick AU - Tan P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/genetics/*metabolism MH - Breast Neoplasms/*genetics/metabolism/mortality MH - Disease Progression MH - Female MH - *Gene Expression Profiling MH - Humans MH - Immunohistochemistry MH - Middle Aged MH - *Oligonucleotide Array Sequence Analysis MH - Receptor, ErbB-2/metabolism EDAT- 2008/01/29 09:00 MHDA- 2008/03/28 09:00 CRDT- 2008/01/29 09:00 PHST- 2008/01/29 09:00 [pubmed] PHST- 2008/03/28 09:00 [medline] PHST- 2008/01/29 09:00 [entrez] AID - 14/2/461 [pii] AID - 10.1158/1078-0432.CCR-07-0999 [doi] PST - ppublish SO - Clin Cancer Res. 2008 Jan 15;14(2):461-9. doi: 10.1158/1078-0432.CCR-07-0999.