Concordancy of immunocytochemistry profiling of circulating tumor cells with immunohistochemistry for analysis of therapeutically relevant biomarkers.

3047 Background: Immunohistochemistry (IHC) profiling of tumor tissue is the present standard for evaluation of therapeutically relevant biomarkers such as ER, PR, HER2, AR, ARv7, PD-L1 and MMR for selection of targeted, endocrine and checkpoint inhibitor therapy selection. However, this critical analysis is dependent on availability of tumor tissue obtained by an invasive biopsy. Challenges to this analysis include insufficient tumor tissue and inability to perform a repeat biopsy to obtain fresh tumor tissue. We have previously described an approach for negative enrichment of Circulating Tumor Cells (CTCs) from peripheral blood and for Immunocytochemistry (ICC) profiling of these CTCs for detection of diagnostically relevant tissue of origin and subtype specific markers, concordant with tumor tissue analysis. Methods: In the present study, we determined concordance between tumor tissue (HPE) and CTCs (ICC) for ascertaining the status of therapeutically relevant markers ER, PR, HER2, AR, ARv7 PD-L1 and MMR. We evaluated 201 matched pairs of tumor tissue (FFPE blocks) and CTCs obtained from peripheral blood. Results: Among the 743 paired assays on matched tumor tissue and CTCs, concordance (positive or negative) was observed in 651 matched pairs (87.6%). The concordance was 82.9% for ER, 100% for PR, 90.2 % for Her2, 93.8% for AR, 90% for Arv7, 85.1% and 87.6% for PD-L1 clones 22c3 and 28-8, and 85.6% for MMR (MLH1, MSH2, MSH6, and PMS2). Conclusions: The study findings indicate that ICC analysis of CTCs may be able to substitute IHC analysis of tumor tissue for profiling of therapeutically relevant markers. This approach may have application in cases where tumor tissue may be limiting and / or where an invasive biopsy to obtain tumor tissue may be unviable.