Primary tumor (p-bx) versus metastatic tumor (m-bx) tissue versus liquid biopsy (lb) in intrahepatic cholangiocarcinoma (IHCC): A comparative comprehensive genomic profiling (CGP) study.
4579 Background: Genomic alterations (GA) characteristic of IHCC are well known. We queried whether GA from Pbx would differ from Mbx and Lbx in IHCC. Methods: Hybrid-capture based CGP was performed on 1,268 tissue samples of advanced stage IHCC using Pbx in 1,048 cases and Mbx from 220 cases and 364 Lbx cases (solid tissue: 318-327 genes, Lbx: 72 genes). Tumor mutational burden (TMB) was determined on 0.8-1.1 Mbp of sequenced DNA. PD-L1 expression in tumor cells (Dako 22C3) was measured by IHC. Results: Mbx sites included: lymph nodes (63), soft tissues (47), peritoneum (34), lung/pleura (27), omentum (15), bone (10), abdomen (7), GYN tract (5), liver (4), brain (2), Upper GI (2), colon (2), bladder (1), and adrenal (1). The GA/sample and biomarkers of immuno-oncology (IO) drug response were similarThe KRAS mutation frequency including G12C alterations was doubled in Mbx compared to Pbx and Lbx (p < 0.001). Frequencies of untargetable GA were similar overall. IDH1 (p < 0.001) and FGFR2 GA known to be enriched in IHCC were less frequent in Mbx than Pbx. Both IDH1 and FGFR2 were identified in Lbx. GA in STK11 (p < 0.001) and SMAD4 (p = 0.0016) were more frequently identified in Mbx. Conclusions: GA found in Pbx vs Mbx and Lbx in IHCC are significantly different; the Mbx cohort features greater KRAS and lower IDH1 and FGFR2 GA. Lbx detected more IDH1 GA than Mbx. This suggests that the Mbx group may contain non-IHCC cases whose metastatic lesions were actually derived from other primary sites and incorrectly assigned the diagnosis of IHCC. [Table: see text]