Abstract
Abstract
Ampullary adenocarcinoma is rare and its immune biomarker landscape is incompletely characterized. This paper evaluated mismatch repair (MMR), programmed death-ligand 1 (PD-L1) and compartment-specific CD3/CD8 tumor-infiltrating lymphocytes (TILs) in resected tumors and explored associations with disease-specific survival (DSS). Ninety-nine patients underwent pancreaticoduodenectomy at Vancouver General Hospital between 1984–2013. Duplicate 0.6-mm tissue microarrays were assessed for MMR proteins, PD-L1 combined positive score (CPS), and stromal and intra-epithelial CD3 and CD8 counts. DSS was estimated by Kaplan–Meier methods. Exploratory Cox models adjusted for age, histologic subtype, pT group, pN status, and adjuvant chemotherapy. There were 44 DSS events. MMR deficiency was present in 37/99 tumors (37.4%). PD-L1 was evaluable in 87 tumors; 57/87 (65.5%) had CPS ≥1 and 24/87 (27.6%) had CPS ≥10. Intraepithelial CD8+ T-cells were present in 23/98 tumors (23.5%). PD-L1 CPS ≥1, PD-L1 CPS ≥10 and MMR status were not associated with DSS by log-rank testing (P=0.35, P=0.98, and P=0.74 respectively). In the pT-adjusted model, intraepithelial CD8 presence was associated with lower disease-specific hazard (HR 0.422; 95% CI 0.144–0.994; likelihood-ratio P=0.048), although the Wald sensitivity test was not significant (P=0.074). Continuous log-transformed intraepithelial CD8 counts showed a concordant, method-dependent signal. dMMR and PD-L1 expression were common in this historical resected cohort. Intraepithelial CD8 infiltration was associated with DSS, but the borderline and inferential-method-dependent estimates require external validation. These prognostic data do not establish benefit from immune checkpoint blockade.