Comprehensive Immuno-Molecular Profiles for Liposarcoma: Roles of Programmed Death Ligand 1, Microsatellite Instability, and PIK3CA

Abstract

<b><i>Background:</i></b> Developing personalized strategies for cancer has shown good efficacies. <b><i>Methods:</i></b> We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and <i>PIK3CA</i>. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and <i>PIK3CA</i> mutation/amplification using pyrosequencing and fluorescence in situ hybridization. <b><i>Results:</i></b> Seventeen (23%) cases were TIL⁺ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL^– tumors (84.4 vs. 60.8%, <i>p</i> = 0.007). Six (35.3%) PD-L1⁺ tumors were detected only in TIL⁺ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. <i>PIK3CA</i> mutation was detected in 7 (9.5%) [exon 9 (<i>n</i> = 4) and exon 20 (<i>n</i> = 3)] and only 1 Q546K mutation was a PD-L1⁺ tumor. <i>PIK3CA</i> copy number gain was detected in 18 (24.4%) and was associated with TIL⁺ tumors (<i>p</i> = 0.045). <b><i>Conclusions:</i></b> Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine.