PD-L1 in a South African cohort of endometrial carcinomas: directions for the future

The Programmed Death-1(PD-1)/Programmed Death Ligand 1 (PD-L1) pathway is the focus of numerous clinical trials on various tumours using immunotherapy. Endometrial tumours with Polymerase E gene mutations and microsatellite unstable neoplasms have demonstrated strong immune responses against mutationally associated neoantigens, with favourable results using immune checkpoint inhibitors. We assessed PD-L1 on endometrioid endometrial carcinomas (EECs) in South Africa’s state hospital sector, which, to the best of our knowledge, has not been investigated. We performed PD-L1 immunohistochemistry on 145 EECs and compared PD-L1 status to our data on cases that had previously undergone mismatch repair (MMR) immunohistochemistry, microsatellite instability assessment by polymerase chain reaction (PCR) and methylation analysis. PD-L1 was expressed in 13.1% (19/145) of EECs, of which, 7 (36.8%) showed MMR deficiency. There was MMR deficiency in 26.9% (34/126) of PD-L1 negative cases (p = 0.37). There were 47.4% (9/19) microsatellite unstable PD-L1 positive cases whereas 52.6% (10/19) of PD-L1 positive cases were microsatellite stable by PCR (p = 0.23). From the PD-L1 positive cases that underwent methylation testing, 80% (8/10) were methylated and 20% (2/10) were unmethylated (p = 0.54). Compared to a Jordanian study and a Chinese study, on populations also not extensively investigated, our study demonstrated lower PD-L1 expression (p = 0.0170; p-value < 0.001 respectively). Our study showed that approximately two-thirds of cases were MMR proficient, which is more than twice the accepted published number of PD-L1 positive cases with MMR staining. This suggests that in our population PD-L1 staining should be considered in all EECs to identify cases that may derive benefit from immune checkpoint inhibitors. It is envisioned that this study may provide the impetus for future possible immune therapies for endometrial cancer patients in the state sector of South Africa. Our study provides data from a developing country which adds to current global data.

PD-L1; Endometrial carcinoma; South Africa

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