Abstract
Non-ampullary duodenal adenocarcinoma (NADC) is extremely rare. Little is known about its clinicopathological and molecular features or its management. Herein we retrospectively analyzed the cases of 32 NADC patients, focusing on microsatellite instability (MSI), genetic mutations, CpG island methylator phenotype (CIMP), and immunostaining including mucin phenotype and PD-L1 expression. The incidence of MSI, KRAS/BRAF/GNAS mutations and CIMP was 51.6%, 34.4%/3.1%/6.5% and 28.1%, respectively. PD-L1 expression was seen in 34.4% of patients. No significant associations between clinicopathological features and KRAS/BRAF/GNAS genetic mutations or CIMP were found. Histologically non-well-differentiated-type NADCs and those in the 1st portion of the duodenum were significantly associated with later stages (stages III–IV) (P = 0.006 and P = 0.003, respectively). Gastric-phenotype NADCs were frequently observed in the 1st portion and in late-stage patients; their cancer cells more frequently expressed PD-L1. Histologically, the non-well-differentiated type was an independent predictor of PD-L1 expression in cancer cells (OR 25.05, P = 0.04) and immune cells (OR 44.14, P = 0.02). Only late-stage disease (HR 12.23, P = 0.01) was a prognostic factor for worse overall survival in a Cox proportional hazards regression model. Our observation of high proportions of MSI and PD-L1 expression may prompt the consideration of immune checkpoint inhibitors as a new treatment option for NADCs.
Highlights
Non-ampullary duodenal adenocarcinoma (NADC) is extremely rare
Mixed gastric (G)-type NADCs were identified in 14 cases (43.8%), comprising 3 gastric phenotype (G-type) and 11 gastric and intestinal phenotype (GI-type) NADCs
The number of programmed cell death-ligand 1 (PD-L1)-positive cases was small, when we evaluated the expression in cancer cells and immune cells separately, only the non-well-differentiated type was a predictive factor of PD-L1 expression in both cancer cells and immune cells (Table 3)
Summary
Male Female Histology Well Moderate Poor Tumor location 1st portion 2nd portion 3rd portion Stage 0–I II III IV Immunohistochemistry Mucin phenotype I–type Mixed G-type HER2 positive Das-1 positive PD-L1 positive (>1%) Tumor cell Immune cell MMR-deficiency† Molecular alterations MSI‡ CIMP KRAS mutated BRAF mutated GNAS mutated‡. The Kaplan-Meier survival analysis demonstrated that the NADCs of the histologically non-well-differentiated type (P < 0.0001), in the 1st portion of the duodenum (P = 0.002), at the late stages (P = 0.0001), with MSI (P = 0.09), and with PD-L1 expression in immune cells (P = 0.05) were associated with worse overall survival (OS) by the log-rank test (Fig. 1), while there were no significant associations between other clinicopathological or molecular features and OS
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