Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 545
© 2005 American Society of Clinical Oncology

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Abstract

Microarray profiling is feasible using archived tissue from a Cooperative Group Clinical Trial: Results from a pilot study in CALGB 9342

Dana-Farber Cancer Inst, Boston, MA; Univ of North Carolina, Chapel Hill, NC; Children’s Hosp, Boston, MA; Duke Univ, Durham, NC; Univ of Chicago, Chicago, IL; Arcturus Inc., Los Angeles, CA; Washington Univ, St Louis, MO

545

Background: CALGB 9342 was designed to test the efficacy of paclitaxel in women with advanced breast cancer. Tissue blocks were collected to retrospectively assess single gene markers (Lin et al, ASCO 2004, Abstract # 9562). RNA profiling has been able to classify tumors into biologic subtypes: ER/PR positive, HER2 amplified and basal-like (ER/PR/HER2 negative) (Perou et al, Nature 2001). To assess the feasibility of performing RNA microarray from this archived material, a pilot study was performed to determine if tumor subtypes could be identified by gene expression profiles. Methods: Primary tumors diagnosed between 1990–97 from women with metastatic breast cancer enrolled on CALGB 9342 were selected. Thirty formalin fixed, paraffin-embedded (FFPE) tissue blocks were selected based on HER2 by FISH (Vysis Pathvysion.), estrogen and progesterone receptor status (from pathology report) to equally represent three categories of breast cancer: HER2 amplified, ER and/or PR positive, ER/PR/HER2 negative. 4 uM tissue sections were macrodissected, RNA was isolated, linearly amplified, hybridized to two microarray platforms (Custom Agilent 22K gene chip, Affymetrix X3P whole genome array) using appropriate labeling methods. Tumors were classified by gene expression pattern using intrinsic signature genes and the ability to predict biomarker status was subsequently determined. Results: Twenty-eight of 30 cases could be successfully amplified and hybridized for microarray profiling. Ten percent of Agilent arrays and 20% of Affymetrix arrays were of poor quality. Both Agilent Whole Genome Chip and the Affymetrix X3P array correctly classified 9/10 HER2 positive, 8/9 ER/PR positive and 9/9 triple negative cases. Neither poor quality nor misclassification could be explained by year of embedding of the primary tumor. Conclusions: Microarray profiling from archived, FFPE tissue from cooperative group clinical trials is able to correctly classify tumor subtypes in the majority of cases. This data suggests that microarray profiling from large cohorts of archived tissue may be feasible to search for gene expression patterns that predict outcome.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Arcturus Arcturus

Abstract presentation from the 2005 ASCO Annual Meeting