Abstract P1-01-17: Integrative pathology: Analysis of cellular multiplex technology to detect proteomic, genomic and DNA data from fine needle aspiration biopsy specimens
Authors: Mittendorf EA , Dogan B , Morgan R , Chargin A , Wu Y , Cornett-Risher S , Shults K 
Published: May 2016

Abstract
Background: An integrative system capable of detecting proteomic, genomic and DNA content from cell isolates obtained by fine needle aspiration (FNA) biopsy may offer distinct advantages in diagnosing breast cancer and monitoring response to therapy. Cellular Multiplex™ is such a system. An initial pilot study evaluating this technology established a series of variables that could separate normal from cancerous elements using cells obtained from an FNA performed on excised tumors and reduction mammoplasty specimens. In order for the technology to be clinically relevant, it must perform robustly on intact tumors. The current study was therefore undertaken to validate Cellular Multiplex™ on cells obtained by FNA performed on intact tumor at the time of diagnosis.
Methods: Patients undergoing lumpectomy requiring either needle or 125I seed localization were identified. FNA was performed on intact tumor (A samples) at the time of radiographic localization prior to lumpectomy and repeated on the excised tumor (B samples). Cells obtained by FNA were placed in a proprietary fixative then hybridized and stained to detect multiple mRNA and protein targets along with DNA content. Estrogen receptor, progesterone receptor and HER2 were included in the panel of targets and compared to the routine clinical pathology report. Cell morphology was assessed by mean corpuscular volume. Samples were analyzed using an EC800 (Sony Biotechnology, San Jose, CA) and the results from matched A and B samples were compared using the Mann-Whitney Wilcoxson Rank Sum test. The study is designed to enroll 50 patients. Here we report an analysis of the first 9 cases.
Results: The cell number obtained from the excised tumors were 3-4 times greater (median to median) than obtained from the intact tumor. There was no statistical difference in the expression of the 2 mRNA targets, 8 protein targets, DNA content and cell morphology between the A and B samples. The parameters derived from Cellular Multiplex matched the standard pathologic features reported on the clinical pathology report in 8 of 9 cases. In the one discrepant case, Cellular Multiplexing detected ER positive cells in a case where standard pathologic evaluation with immunohistochemistry reported the tumor to be estrogen receptor negative.
Conclusions: This interim analysis demonstrates that the Cellular Multiplex technology is working well using cells obtained by FNA performed on intact tumors with readouts matching those obtained from excised specimens. If confirmed in the remaining patients, these data suggest that this technology will be applicable for the evaluation of intact tumors thereby making it relevant for multiple clinical indications including diagnosis and monitoring response to neoadjuvant therapy.
Citation Format: Mittendorf EA, Dogan B, Morgan R, Chargin A, Wu Y, Cornett-Risher S, Shults K. Integrative pathology: Analysis of cellular multiplex technology to detect proteomic, genomic and DNA data from fine needle aspiration biopsy specimens. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-17.