PD-L1 expression in endocervical adenocarcinoma correlation with patterns of tumor invasion, CD8⁺ tumor-infiltrating lymphocytes, and clinical outcomes

Programmed death-1 ligand (PD-L1) expression has been used as a predictive marker for response to immune checkpoint inhibitors and has been reported to have prognostic value. Its prevalence and significance in endocervical adenocarcinoma (ECA) remain underinvestigated. We evaluated PD-L1 expression and CD8⁺ tumor-infiltrating lymphocyte density in whole tissue sections of 89 ECAs. PD-L1 expression was observed in 68% of ECAs by combined positive score (CPS, cutoff 1) and 29% of ECAs by tumor proportion score (TPS, cutoff 1%). Using CPS, PD-L1 expression was seen in 11%, 78%, and 72% of pattern A, B, and C tumors, respectively, with significantly higher expression in tumors with destructive-type invasion (B and C) (P = 0.001 [A vs. B], 0.0006 [A vs. C], 0.0002 [A vs. B+C]). Using TPS, no significant difference in PDL1 expression was seen between tumors with different invasion patterns (0%, 22%, and 32% in tumors with pattern A, B, and C, respectively; P = 0.27 [A vs. B], 0.053 [A vs. C], 0.11 [A vs. B+C]). PD-L1-positive ECAs demonstrated significantly higher CD8⁺ tumor-infiltrating lymphocyte density (CPS: P = 0.028; TPS: P = 0.013) and worse progression-free survival when compared with PD-L1-negative ECAs (CPS: hazard ratio [HR] = 4.253 vs. 0.235, P = 0.025; TPS: HR = 4.98 vs. 0.2; P = 0.004). When invasion patterns were separately assessed, pattern C tumors similarly showed worse progression-free survival in PD-L1-positive tumors (CPS: HR = 6.15 vs. 0.16, P = 0.045; TPS: HR = 3.78 vs. 0.26, P = 0.027). In conclusion, our data show frequent PD-L1 expression in ECA with destructive-type invasion, supporting the role of the PD-1/PDL1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome.