Abstract
BackgroundDetermining the primary site of metastatic cancer with confidence can be challenging. Pathologists commonly use a battery of immunohistochemical (IHC) stains to determine the primary site. Gene expression profiling (GEP) has found increasing use, particularly in the most difficult cases. In this pilot study, a direct comparison between GEP and IHC-guided methods was performed.MethodsTen archived formalin-fixed paraffin embedded metastatic tumor samples for which the primary site had been clinically determined were selected. Five pathologists who were blinded to the diagnosis were asked to determine the primary site using IHC and other stains selected from a panel of 84 stains. Each pathologist was provided patient sex, biopsy site and gross sample description only. Slides were digitized using ScanScope®XT at 0.25 μm/pixel. Each evaluating pathologist was allowed to provide a diagnosis in three stages: initial (after reviewing the H&E image), intermediate (after reviewing images from the first batch of stains) and final diagnosis (after the second batch of stains if requested). GEP was performed using the only FDA-cleared test for this intended use, the Pathwork Tissue of Origin Test. No sample information was provided for GEP testing except for patient sex. Results were reported as the tumor tissue type with the highest similarity score.ResultsIn this feasibility study, GEP determined the correct primary site in 9 of the 10 cases (90%), compared to the IHC-guided method which determined the correct primary site for 32 of 50 case evaluations (average 64%, range 50% to 80%). The five pathologists directing the IHC-guided method ordered an average of 8.8 stains per case (range 1 to 18). GEP required an average of 3 slides per case (range 1 to 4).ConclusionsResults of the pilot study suggest that GEP provides correct primary site identification in a higher percentage of metastatic cases than IHC-guided methods, and uses less tissue. A larger comparative effectiveness study using this study design is needed to confirm the results.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1749854104745508
Highlights
Determining the primary site of metastatic cancer with confidence can be challenging
The determination of primary site was based on all available clinical information, but was not accepted when the diagnosis was made exclusively using immunohistochemistry (IHC) or special stains. (ii) All tumor samples were selected from a panel of 15 tumor tissue types covered by the Tissue of Origin Test
From among the 442 total stains ordered by all the evaluating pathologist (EP) for all the cases, an average of 22 unique stains per case was ordered by the group of five EPs
Summary
Determining the primary site of metastatic cancer with confidence can be challenging. Pathologists commonly use a battery of immunohistochemical (IHC) stains to determine the primary site. Gene expression profiling (GEP) has found increasing use, in the most difficult cases. Gene expression profiling (GEP) tests and tests using microRNA markers have been developed to aid in the diagnosis of difficult-to-diagnose tumors [9,10,11]. These tests use formalin-fixed paraffin-embedded (FFPE) tissue and either microarrays or real-time polymerase chain reaction technologies to measure levels of multiple markers followed by application of an algorithm to predict the most likely primary site for a particular sample
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