1505P - Analysis of expression of immunomodulation factors in alveolar soft-part sarcoma: a retrospective study from the Spanish Group for Research on Sarcoma (GEIS)

Abstract

Background: Alveolar soft-part sarcoma (ASPS) is an exceedingly rare entity. We previously reported on a series of 12 ASPS the expression of PD-1/PD-L1 and lymphocytic infiltrates. PD-L1 staining was positive in 50% of the cases, suggesting a role for immunomodulatory interventions. We now enlarge the series and explore the expression of immune-related genes with the HTG EdgeSeq System and analyze their possible prognostic role. Methods: Patients (pts) diagnosed with ASPS from Dec 1994 to Jul 2016 were reviewed. Clinical characteristics and outcome were collected. Immunohistochemical expression was tested on archived Formalin-Fixed Paraffin-Embedded (FFPE) blocks using PD-L1 (ab205921; Abcam), CD8 (ab4055; Abcam) antibodies. An ImmunOncology (IO) panel of 549 mRNAs was evaluated with the HTG EdgeSeq System from one 5µm FFPE section. This novel technology consists in a tissue digestion followed by a pre-hybridization with specific probes using quantitative nuclease protection assay (qNPA) and quantified by a standard RNA-seq protocol in a NGS sequencer. Results: We identified 16 ASPS pts: median age 23y (6-62), M/F=5/11. Stage localized/metastatic in 11/5. With a median FU of 91 mos (4-151), 6/11 pts (54%) relapsed, with a median RFS of 19 mos (95% CI 1-75) and 2 pts died. PD-L1 was pos in tumor in 10/16 (62%) pts. HTG showed differential expression of immune-related genes according to stage (localized vs metastatic) in MNDA (log2 fold change: -3.01, p < 0.00001) and PRAME (log2 fold change: 1.9, p < 0.0002). Pts relapsing differentially expressed ABCC2 (log2 fold change -1,64, p < 0.04) when compared with those not relapsing. PD-L1 pos vs neg tumors (pos>5% membrane staining for PD-L1) differentially expressed TNFSF11 (fold change: -1,77, p = 0.05). Tumors infiltrated/not for CD8 lymphs (pos>10% of CD8) had a differential expression of CCL18 (log2 fold change: 4,89, p < 0.0001) and SLAMF7 (log2 fold change 2,37, p < 0.0089). Conclusions: PD-L1 is expressed in more than a half of ASPS of our series. Differential expression in immune-associated genes suggest an immune related gene profile on this entity with clinical and pathological implications. Further exploration of immune-modulation in ASPS is ongoing. Legal entity responsible for the study: Spanish Group for Research on Sarcoma Funding: Spanish Group for Research on Sarcoma (GEIS). Disclosure: All authors have declared no conflicts of interest.