Introduction Invasive stratified mucin-producing carcinoma (ISMC) is a rare histological type of human papillomavirus-associated (HPVA) mucinous-type endocervical adenocarcinoma (EAC). Compared to other HPVA EACs, ISMC shows more frequent post-treatment recurrences and metastases as well as worse survival. We investigated the differences in clinicopathological characteristics, patient outcomes, and programmed death-ligand 1 (PD-L1) expression status among ISMC, usual-type EAC (UEA), and gastric-type EAC (GEA).

Methods PD-L1 22C3 immunostaining was performed using 20 ISMCs, 20 UEAs, and 20 GEAs. PD-L1 expression was assessed using combined positive score (CPS). We examined whether there are significant differences in clinicopathological characteristics and PD-L1 expression status among ISMC, UEA, and GEA.

Results ISMC showed significantly younger age, more advanced stage, and shorter survival than UEA. Recurrence-free and overall survival rates of ISMC patients were comparable to those of GEA and significantly lower than those of UEA. All 20 ISMCs showed PD-L1 over-expression with a mean CPS of 43.5 (range=10–100), which was significantly higher than that of UEA (mean CPS=8.2; p=0.017) and GEA (mean CPS=6.5; p=0.004). In spite of PD-L1 over-expression, ISMC patients who treated with pembrolizumab showed no clinical responses. PD-L1 overexpression was found to be a significant predictor for RFS and OS in patients with ISMC. All examined ISMCs over-expressed PD-L1.

Conclusion/Implications All examined ISMCs over-expressed PD-L1. ISMC showed significantly higher PD-L1 expression than other EACs and worse survival than UEA. Our data suggest that PD-L1 over-expression is associated with poor prognosis of ISMC.