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Molecular alterations and PD-L1 expression in non-ampullary duodenal adenocarcinoma: Associations among clinicopathological, immunophenotypic and molecular features
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
- Publication Year :
- 2019
-
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.
- Subjects :
- 0301 basic medicine
Male
lcsh:Medicine
Kaplan-Meier Estimate
medicine.disease_cause
Gastroenterology
B7-H1 Antigen
Prognostic markers
0302 clinical medicine
Duodenal Neoplasms
GTP-Binding Protein alpha Subunits, Gs
lcsh:Science
Multidisciplinary
biology
Molecular medicine
DNA, Neoplasm
Middle Aged
Prognosis
Phenotype
3. Good health
Neoplasm Proteins
Female
Microsatellite Instability
KRAS
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Adenocarcinoma
Article
03 medical and health sciences
Gastrointestinal cancer
Internal medicine
medicine
GNAS complex locus
Chromogranins
Humans
neoplasms
Aged
Proportional Hazards Models
Retrospective Studies
CpG Island Methylator Phenotype
Proportional hazards model
business.industry
lcsh:R
Microsatellite instability
DNA Methylation
medicine.disease
digestive system diseases
030104 developmental biology
Genes, ras
Risk factors
Cancer cell
Mutation
biology.protein
lcsh:Q
Duodenal adenocarcinoma
CpG Islands
business
030217 neurology & neurosurgery
Genes, Neoplasm
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....697b8b4a1c71b9dc24f78173f78a2907