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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-07-19

AUTHORS

Jiro Watari, Seiichiro Mitani, Chiyomi Ito, Katsuyuki Tozawa, Toshihiko Tomita, Tadayuki Oshima, Hirokazu Fukui, Shigenori Kadowaki, Seiji Natsume, Yoshiki Senda, Masahiro Tajika, Kazuo Hara, Yasushi Yatabe, Yasuhiro Shimizu, Kei Muro, Takeshi Morimoto, Seiichi Hirota, Kiron M. Das, Hiroto Miwa

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. More... »

PAGES

10526

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  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    9

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-46167-y

    DOI

    http://dx.doi.org/10.1038/s41598-019-46167-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1118097789

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31324814


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