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Distinct immunological properties of the two histological subtypes of adenocarcinoma of the ampulla of Vater

Authors
 Min Hwan Kim  ;  Mi Jang  ;  Hoguen Kim  ;  Woo Jung Lee  ;  Chang Moo Kang  ;  Hye Jin Choi 
Citation
 CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol.68(3) : 443-454, 2019 
Journal Title
CANCER IMMUNOLOGY IMMUNOTHERAPY
ISSN
 0340-7004 
Issue Date
2019
MeSH
Adenocarcinoma/immunology* ; Adenocarcinoma/mortality ; Adenocarcinoma/pathology ; Aged ; Ampulla of Vater* ; B7-H1 Antigen/analysis ; CD8-Positive T-Lymphocytes/immunology ; Common Bile Duct Neoplasms/immunology* ; Common Bile Duct Neoplasms/mortality ; Common Bile Duct Neoplasms/pathology ; Female ; Humans ; Immunohistochemistry ; Lymphocyte Count ; Male ; Middle Aged ; Nuclear Proteins/analysis ; Prognosis ; Proportional Hazards Models ; Transcription Factors/analysis
Keywords
Adenocarcinoma of the ampulla of Vater ; CD8 T lymphocytes ; Immunohistochemistry ; PD-L1 ; Prognosis ; YAP
Abstract
Adenocarcinoma of the ampulla of Vater (AOV) is classified into intestinal type (IT) and pancreatobiliary type (PB); however, the immunological properties of these subtypes remain to be characterized. Here, we evaluated the clinical implications of PD-L1 expression and CD8+ T lymphocyte density in adenocarcinomas of the AOV and their potential association with Yes-associated protein (YAP). We analyzed 123 adenocarcinoma-of-the-AOV patients who underwent surgical resection, and tumors were classified into IT or PB type. Tumor or inflammatory cell PD-L1 expression, CD8+ T lymphocyte density in the cancer cell nest (intratumoral) or in the adjacent stroma, and YAP localization and intensity were analyzed using immunohistochemical staining. PB-type tumors showed higher tumoral PD-L1 expression than IT-type tumors, and tumoral PD-L1 expression was associated with a shorter disease-free survival (DFS) [hazard ratio (HR), 1.77; p = 0.045] and overall survival (OS) (HR 1.99; p = 0.030). Intratumoral CD8+ T lymphocyte density was higher in IT type than in PB type and was associated with a favorable DFS (HR 0.47; p = 0.022). The nuclear staining pattern of YAP in tumor cells, compared to non-nuclear staining patterns, was more frequently associated with PB type and increased tumoral PD-L1 expression. Nuclear YAP staining was a significant prognostic factor for OS (HR 2.21; p = 0.022). These results show that the two subtypes of adenocarcinoma of the AOV exhibit significant differences in tumoral PD-L1 expression and intratumoral CD8+ T lymphocyte density, which might contribute to their distinct clinical features.
Full Text
https://link.springer.com/article/10.1007%2Fs00262-018-02293-6
DOI
10.1007/s00262-018-02293-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Jang, Mi(장미) ORCID logo https://orcid.org/0000-0002-0153-9847
Choi, Hye Jin(최혜진) ORCID logo https://orcid.org/0000-0001-5917-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/169400
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