Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
Clin Transl Gastroenterol. 2021 Nov 18;12(11):e00424. doi: 10.14309/ctg.0000000000000424.
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.
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.
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.
Only KRAS mutation was a significant prognostic factor in primary sporadic nonampullary duodenal adenocarcinoma in cases in which TNM stage was considered.
原发性非壶腹十二指肠腺癌的基因组特征表明其与胃和结直肠癌具有遗传相似性。然而，这些癌症的临床和分子特征之间尚未建立相关性。本研究旨在阐明散发性非壶腹十二指肠上皮性肿瘤的临床病理特征，包括其分子特征和预后因素。
本研究共检查了 148 例散发性非壶腹十二指肠上皮性肿瘤患者。评估了患者的性别、年龄、TNM 分期、肿瘤部位、治疗方法、组织学、KRAS 突变、BRAF 突变、具核梭杆菌、黏蛋白表型和程序性死亡配体 1（PD-L1）状态。通过直接测序、实时定量聚合酶链反应和免疫化学染色分析 KRAS 和 BRAF 突变、具核梭杆菌、黏蛋白表型和 PD-L1 状态。
中位随访时间为 119.4 个月。十二指肠腺瘤（原发性疾病）无死亡病例。十二指肠腺癌的 Kaplan-Meier 分析显示 TNM 分期有显著影响（P < 0.01）。在原发性十二指肠腺癌死亡的单因素分析中，TNM 分期Ⅱ期或更高、未分化、KRAS 突变、胃表型、肠表型和 PD-L1 状态是显著因素。在多因素分析中，TNM 分期Ⅱ期或更高（危险比：1.63×1010，95%置信区间：18.66-6.69×1036）和 KRAS 突变（危险比：3.49，置信区间：1.52-7.91）是显著因素。
仅 KRAS 突变是考虑 TNM 分期时原发性散发性非壶腹十二指肠腺癌的显著预后因素。
