Distinct immunological properties of the two histological subtypes of adenocarcinoma of the ampulla of Vater
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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.
KeywordsAdenocarcinoma of the ampulla of Vater PD-L1 CD8 T lymphocytes YAP Prognosis Immunohistochemistry
American Joint Committee on Cancer
Ampulla of Vater
Myeloid-derived suppressor cells
MHK, MJ, HK, CMK, and HJC conceived the study. MJ and HK performed and interpreted the pathologic review. Clinical data collection and interpretation were done by MHK, CMK, WJL, and HJC. MHK, MJ, CMK, and HJC wrote the manuscript.
This study was supported by a Grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA16C0018) and by a faculty research Grant for Yonsei University College of Medicine for 2015 (6-2015-0053).
Compliance with ethical standards
Conflict of interest
The authors declare no potential conflicts of interest.
This study was reviewed and approved by the Institutional Review Board of Severance Hospital, Seoul, Korea (approval number: 4-2017-0542).
Informed consent was obtained from all patients at the time of surgery for the analysis of tumor specimens used for investigations. The requirement for informed consent for the retrospective study was waived by the Institutional Review Board, because this study was performed more than 5 years after the surgery and acquisition of the tumor tissues.
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