十二指腸
原発性非乳頭部十二指腸癌の臨床病理学的・分子病理学的検討
- 演 者：
- 渡 二郎1，三谷 誠一郎2, 戸澤 勝之1, 富田 寿彦1, 大島 忠之1, 福井 広一1, 門脇 重憲2,
夏目 誠治3, 千田 嘉毅3, 田近 正洋4, 原 和生5, 谷田部 恭6, 清水 泰博3, 廣田 誠一7, 三輪 洋人1 - 所属機関：
- 1兵庫医科大学・消化管科, 2愛知県がんセンター中央病院・薬物療法部, 3愛知県がんセンター中央病院・消化器外科, 4愛知県がんセンター中央病院・内視鏡部, 5愛知県がんセンター中央病院・消化器内科, 6愛知県がんセンター中央病院・遺伝子病理診断部, 7兵庫医科大学・病院病理部
Background: Non-ampullary duodenal carcinoma (NADC) is extremely rare, and little is known about its clinicopathological features and molecular events. The aims of this study were to clarify (1) the clinicopathological features of and (2) molecular events occurring in NADC carcinogenesis.
Methods: Microsatellite instability (MSI), CpG island methylation in 7 tumor-associated genes, the phenotype (CIMP), KRAS/BRAF/GNAS mutations, and immunostain of PD-L1 in 32 NADC patients, comprising stage 0-II in 19 and stage III-IV in 13, were analyzed. Mucin phenotype was also analyzed and divided into 2 categories: the gastric-mixed phenotype (G-type) and the intestinal phenotype (I-type). Promoter methylation was assessed using methylation-sensitive high-resolution melting analysis.
Results: 1) Incidences of MSI, CIMP, and KRAS/BRAF/GNAS mutations were 61.3%, 28.1%, and 34.4%/3.1%/6.5%, respectively. However, 2) no significant associations between clinicopathological features and MSI, CIMP, or KRAS/BRAF/GNAS mutations were found. 3) NADCs located in the 1st portion of the duodenum were more frequently in the advanced stages (stages III-IV) compared with those in the 2nd and 3rd portion (p=0.0003). 4) G-type NADC tended to be observed in the 1st portion and were in the advanced stages (p=0.09 for each). 5) A significantly higher proportion of histologically moderate to poorly differentiated NADCs were of the advanced stage (p=0.003). 6) There was no significant association between MSI and PD-L1 expression. 7) Positive PD-L1 expression was significantly associated with histologically moderately to poorly differentiated NADCs (p=0.0006), I-type (p=0.04), and advanced stage (p=0.01).
Conclusions: NADCs in the 1st portion of the duodenum, of the G-type, and histologically moderately to poorly differentiated were frequently in the advanced stages. PD-L1 expression was associated with the histology, mucin phenotype, and tumor stage, but was not associated with molecular alterations.
