The Impact of KRAS Mutation in Patients With Sporadic Nonampullary Duodenal Epithelial Tumors

Clin Transl Gastroenterol. 2021 Nov 18;12(11):e00424. doi: 10.14309/ctg.0000000000000424.

Abstract

Introduction: The genomic characterization of primary nonampullary duodenal adenocarcinoma indicates a genetic resemblance to gastric and colorectal cancers. However, a correlation between the clinical and molecular characteristics of these cancers has not been established. This study aimed to elucidate the clinicopathological features of sporadic nonampullary duodenal epithelial tumors, including their molecular characteristics and prognostic factors.

Methods: One hundred forty-eight patients with sporadic nonampullary duodenal epithelial tumors were examined in this study. Patient sex, age, TNM stage, tumor location, treatment methods, histology, KRAS mutation, BRAF mutation, Fusobacterium nucleatum, mucin phenotype, and programmed death-ligand 1 (PD-L1) status were evaluated. KRAS and BRAF mutations, Fusobacterium nucleatum, mucin phenotype, and PD-L1 status were analyzed by direct sequencing, quantitative polymerase chain reaction, and immunochemical staining.

Results: The median follow-up duration was 119.4 months. There were no deaths from duodenal adenoma (the primary disease). Kaplan-Meier analysis for duodenal adenocarcinoma showed a significant effect of TNM stage (P < 0.01). In univariate analysis of primary deaths from duodenal adenocarcinoma, TNM stage II or higher, undifferentiated, KRAS mutations, gastric phenotype, intestinal phenotype, and PD-L1 status were significant factors. In multivariate analysis, TNM stage II or higher (hazard ratio: 1.63 × 1010, 95% confidence interval: 18.66-6.69 × 1036) and KRAS mutation (hazard ratio: 3.49, confidence interval: 1.52-7.91) were significant factors.

Discussion: Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / microbiology
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / analysis
  • Duodenal Neoplasms / genetics*
  • Duodenal Neoplasms / microbiology
  • Duodenal Neoplasms / pathology
  • Female
  • Fusobacterium nucleatum / isolation & purification
  • Gastric Mucosa / pathology
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Phenotype
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • KRAS protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)