[411] Performance of a Gene Expression Microarray Assay To Determine Tissue of Origin in Cytology Body Fluid Specimens.

Federico A Monzon, Gregory A Stancel, Karla Alvarez, Todd Fairley, Dina Mody, Donna Coffey. The Methodist Hospital, Houston, TX; The Methodist Hospital Research Institute, Houston, TX

Background: Identification of the tissue of origin is a common challenge for cytology specimens. Cytologic body fluids are routinely obtained in the diagnostic workup of cases with a metastatic tumor of uncertain origin. The Pathwork Tissue of Origin (TOO) test was recently cleared by the FDA as an in vitro diagnostic device for formalin-fixed paraffin-embedded (FFPE) tissue. We evaluated the performance of this assay in body fluid specimens, including a comparison between specimens preserved with thrombin and CellientTM cell block methodologies.
Design: 37 body fluid specimens (29 metastases-positive and 8 metastases-negative) were tested; 8 of these had both thrombin (T) and Cellient (C) cell blocks (Total n=45). RNA was extracted from 10 micron sections and gene expression assays were performed according to a standardized protocol (Pathwork Diagnostics, Redwood City, CA). A Tissue of Origin report was generated for each sample, and compared with that of the reference diagnosis. In addition, results between the thrombin and Cellient cell block methods were compared.
Results: 7 samples were excluded due to an estimated tumor content of <60% after Pathologist's review. From the remaining 38 samples, 95% achieved successful labeling/amplification. Only 2 samples failed array data quality verification. Therefore, 34 of 38 specimens (89%) successfully yielded test results. All metastases-negative cases but one, showed an expression profile that was most similar to lymphoma, in agreement with the predominant presence of inflammatory cells. TOO results for 16/20 specimens with malignant cells (80%, T/C duplicates not counted) were concordant with the reference diagnosis. Upon review of clinical history, one discordant case originally reported as breast was confirmed as an ovarian metastasis, improving the agreement with reference diagnosis to 85%. Thrombin and Cellient block results were concordant in all cases.
Conclusions: Our results show that it is possible to obtain gene expression profiles from FFPE body fluid specimens using the FFPE version of the Pathwork Tissue of Origin test, when samples meet the >60% tumor content criteria. These results demonstrate that gene expression profiling in body fluid cytology specimens has similar performance characteristics to those obtained in FFPE tissue samples. Pathologist interpretation is important for fluid specimens since negative samples will yield a lymphoma result that is reflective of an inflammatory infiltrate.
Category: Cytopathology

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 73, Wednesday Afternoon


Close Window