Correlative studies
tumour, Cancer
CPS, TUMOUR, CANCER
Formalin fixed, paraffin-embedded (FFPE) sections of archival tumour tissue were used. Haematoxylin & eosin (H&E) and immunohistochemistry (IHC) stains were examined (Supplementary Fig. The H&E- and IHC-stained slides were assessed by a gynaecology expert pathologist blinded to clinical data. A second pathologist examined equivocal cases to reach consensus. PD-L1 expression was defined as complete or partial membrane staining in tumour cells (TC) and membranous and/or cytoplasmic staining in immune cells (IC) – namely, lymphocytes and macrophages. We determined the percentage of positive TCs and ICs in combination, using the combined positive score (CPS). CPS was derived by dividing the total number of PD-L1 positive cells (TCs and ICs) by the number of viable TCs and multiplying by 100. The cut-off value for positive PD-L1 staining was set at 1%. Normal tonsil was used as positive control. For p53, strong positive nuclear expression in >80% of TCs (overexpression pattern) and complete loss of expression in TCs with a positive non-tumour internal control (null pattern) were considered mutation-type. Wild-type (normal) expression was defined as heterogeneous weak to moderate staining. PTEN was scored as either retained (staining of similar intensity seen in TCs relative to non-tumour internal control) or complete absence (negative PTEN staining in TCs with retained expression in non-tumour internal control). MMR protein status was considered deficient (MMRd) when the tumour showed complete loss of nuclear expression in any MMR protein (MLH1, PMS2, MSH2, MSH6). Stromal cells, inflammatory cells and non-tumour epithelial cells served as internal control for MMR, similar to p53 and PTEN.Tumour genomic profiling was conducted as part of two correlative studies (NCT03420118, NCT02906943). A multigene targeted panel spanning exonic regions of 555 cancer-related genes (UHN Hi5 Panel) at the College of American Pathologists/Clinical Laboratory Improvement Amendment (CAP/CLIA)-accredited Advanced Molecular Diagnostics Laboratory (AMDL) at Princess Margaret Cancer CentreThe ctDNA analysis was performed as part of LIBERATE (NCT03702309) study. Extraction of ctDNA was performed from baseline plasma samples and analyzed using a custom designed panel. Exonic coding regions and ±20 bp of the intron for the following genes (