When To Use Gene Expression Profiling? A Direct Comparison with Immunohistochemistry for Diagnosing the Primary Site in Metastatic Cancer
Charles R Handorf, Anand Kulkarni, James P Grenert, Lawrence M Weiss, William M Rogers, Oliver S Kim, Federico A Monzon, Meredith Halks-Miller, Glenda G Anderson, Michael G Walker, Raji Pillai, W David Henner. University of Tennessee College of Medicine, Memphis, TN; University of California San Francisco, San Francisco, CA; Clarient Inc., Aliso Viejo, CA; El Camino Hospital, Mountain View, CA; Advocate Good Shepherd Hospital, Barrington, IL; Baylor College of Medicine, Houston, TX; Pathwork Diagnostics, Redwood City, CA; DegreesBiosciences, San Jose, CA; WalkerBioscience, Carlsbad, CA
Background: Pathologists commonly use a battery of immunohistochemical (IHC) stains to determine the primary site of metastatic cancers. Gene expression profiling (GEP – Pathwork Tissue of Origin Test), is an alternative method for evaluating these cases. We directly compared the accuracy of IHC and GEP and identified subgroups where GEP is most beneficial.
Design: This prospectively conducted, blinded, multicenter study compared the diagnostic accuracy of GEP and IHC in 157 formalin-fixed paraffin-embedded specimens from metastatic tumors with known on-panel primaries in order to have a gold standard to compare diagnostic accuracy. Four pathologists selected from 84 stains in two rounds to render diagnoses. Conditional logistic regression was used to compare the results from the two methods.
Results: 157 samples were evaluated by both IHC and GEP. The GEP test results were more accurate at identifying the primary site for metastatic tumors (89%) than IHC (83%) (p=0.013). GEP was substantially more accurate (94%) than IHC-based diagnoses (79%) in 51 poorly differentiated or undifferentiated samples (p=0.016). The difference was most pronounced in 33 poorly differentiated carcinomas, 91% for GEP vs. 71% for IHC (p=0.022). In samples for which pathologists rendered their final diagnosis with a single round of stains, both IHC and GEP exceeded 90% accuracy. However, when the diagnosis required a 2nd round, IHC significantly underperformed GEP (67% to 83%, P<0.001). When 6 or more first round stains were used, GEP was more accurate than IHC (88% vs. 79% respectively, p=0.012).
Conclusions: The GEP test used in this study was significantly more accurate than IHC when used to identify primary site with the most pronounced superiority observed in specimens that required a 2nd round of stains, 6 or more stains in the first round, and in poorly differentiated and undifferentiated metastatic carcinomas.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 225, Tuesday Morning