Molecular alterations and PD-L1 expression in non-ampullary duodenal adenocarcinoma: Associations among clinicopathological, immunophenotypic and molecular features

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.

Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer

“…R201C resulted in the loss of GTP enzyme activity, the continuous activation of downstream signals, cellular proliferation and tumor formation. Studies have also shown that the mutation rate of GNAS in non-ampullary duodenal adenocarcinoma is 6.5% [ 36 ]. However, GNAS mutations have been more extensively studied in tumors of the pancreatic and biliary system than in GC.…”

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

“…In a mouse model, R201C resulted in the loss of GTP enzyme activity, the continuous activation of downstream signals, cellular proliferation and tumor formation. Studies have also shown that the mutation rate of GNAS in non-ampullary duodenal adenocarcinoma is 6.5% [37]. However, GNAS mutations have been more extensively studied in tumors of the pancreatic and biliary system than in GC.…”

Clinicopathological Features of Epstein-Barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in Chinese Patients with Gastric Cancer

“…R201C resulted in the loss of GTP enzyme activity, the continuous activation of downstream signals, cellular proliferation and tumor formation. Studies have also shown that the mutation rate of GNAS in non-ampullary duodenal adenocarcinoma is 6.5% [37]. However, GNAS mutations have been more extensively studied in tumors of the pancreatic and biliary system than in GC.…”