PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

Abstract

Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones – QR1 and E1L3N – with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.

Biomarkers expression among paired serous ovarian cancer primary lesions and their peritoneal cavity metastases in treatment‐naïve patients: A single‐center study

“…Accumulating evidence suggests that, in OC, PD‐L1 is mostly expressed in tumor‐associated macrophages (TAMs), while IHC labeling of tumor cells is relatively uncommon 27,52 . Our study agrees with Eymerit‐Morin et al, who reported that PD‐L1 tumor cell labeling in OC is an uncommon event and a TPS score > 1%, using the E1L3N antibody, was found in just 14% of their cases 35 . Webb et al also reported PD‐L1 tumor cell positivity in just 13.2% of the tested OC cases, while TAMs were labeled in most of their cases 52 .…”

“…27,52 Our study agrees with Eymerit-Morin et al, who reported that PD-L1 tumor cell labeling in OC is an uncommon event and a TPS score > 1%, using the E1L3N antibody, was found in just 14% of their cases. 35 Webb et al also reported PD-L1 tumor cell positivity in just 13.2% of the tested OC cases, while TAMs were labeled in most of their cases. 52 Three recent studies correlated PD-L1 immunohistochemical status between primary OC lesions and their paired metastases (Table 3); all of them utilized tissue rather than cytologic samples.…”

“…33,34 PD-L1 scoring was performed using the Tumor Proportion Score (TPS) for both E1L3N and 22C3 antibodies and classified as TPS < 1% and TPS > 1%, respectively. 35 All slides were scanned with the Aperio Digital Pathology Slide Scanner AT2 (Leica Biosystems), while the QuPath platform for bioimage analysis was used to evaluate all immunostains. 36 The IHC expression of EGFR, HER2, CD147, and PD-L1 was compared between the primary and their paired metastases with Fisher's exact test.…”

“…A semi‐quantitative “H‐score” was used to evaluate the CD147 membranous immunostaining, taking into account both staining intensity and percentage of cells at each intensity level (formula: [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]), and ranging from 0 to 300 33,34 . PD‐L1 scoring was performed using the Tumor Proportion Score (TPS) for both E1L3N and 22C3 antibodies and classified as TPS < 1% and TPS > 1%, respectively 35 . All slides were scanned with the Aperio Digital Pathology Slide Scanner AT2 (Leica Biosystems), while the QuPath platform for bioimage analysis was used to evaluate all immunostains 36 .…”

Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy

“…To date, there are no recommendations for evaluating immunohistochemical PD-L1 expression for targeted therapy in the first-line treatment of OCs (INCa). 30 But some studies confirm the rationale for using immunotherapy in ovarian cancer patients. PD-1/PD-L1 expression in OC is the main rationale for using immunotherapy in this malignancy.…”