Detecting FLI1 Fusion by Immunohistochemistry (IHC) Stain in Prostatic Adenocarcinoma

Objectives The most common genetic alterations in prostate cancer are fusions of ERG and other members of the E26 transformation-specific (ETS) family of transcription factors, including ETV1, ETV4, and FLI1. Analyzing TCGA data, we found that similar to ERG fusion, FLI1 fusion-associated FLI1 mRNA level increases. ERG IHC stain has been a surrogate test for ERG fusion. Therefore, we hypothesize that FLI IHC stain could also be used to detect FLI1 fusion in prostate cancer. Methods In total, 111 primary prostate adenocarcinoma (>10% by volume) cases from our institute were selected for tissue microarray (TMA) construction. The regular full section slides and TMA slides were subject to IHC stain of ERG and FLI1 (Santa Cruz, SC-113). The criteria for positive FLI1 are (1) nuclear staining; (2) only in tumor cells, not in nontumor cells; and (3) FLI1-positive cells should be negative for ERG IHC staining. Results For prostate TMA slides, ~50% of cases were positive for ERG; ~30% of cases were weakly positive for FLI1. However, all of the FLI1 weakly positive cases were positive for ERG as well possibly due to cross-reactivity between ERG and FLI1, which was demonstrated in other studies. Conclusion Overall, we conclude that the cross-reactivity between FL1 and ERG precluded the detection of FLI1 fusion in prostatic adenocarcinoma under current conditions. We are in the process of selecting some cases to detect FLI1 fusion by next-generation sequencing (NGS) and FISH.