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Cancer Immunology, Immunotherapy

, Volume 68, Issue 3, pp 443–454 | Cite as

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

  • Min Hwan Kim
  • Mi Jang
  • Hoguen Kim
  • Woo Jung Lee
  • Chang Moo KangEmail author
  • Hye Jin ChoiEmail author
Original Article
  • 124 Downloads

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.

Keywords

Adenocarcinoma of the ampulla of Vater PD-L1 CD8 T lymphocytes YAP Prognosis Immunohistochemistry 

Abbreviations

AJCC

American Joint Committee on Cancer

AOV

Ampulla of Vater

DFS

Disease-free survival

IHC

Immunohistochemical

IT

Intestinal

MDSC

Myeloid-derived suppressor cells

OS

Overall survival

PB

Pancreatobiliary

YAP

Yes-associated protein

Notes

Author contributions

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.

Funding

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.

Ethical approval

This study was reviewed and approved by the Institutional Review Board of Severance Hospital, Seoul, Korea (approval number: 4-2017-0542).

Informed consent

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.

Supplementary material

262_2018_2293_MOESM1_ESM.pdf (693 kb)
Supplementary material 1 (PDF 692 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Medical Oncology, Department of Internal MedicineYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Pancreaticobiliary Cancer ClinicYonsei Cancer Center, Severance HospitalSeoulRepublic of Korea
  3. 3.Department of PathologyYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Division of Hepatobiliary and Pancreatic Surgery, Department of SurgeryYonsei University College of MedicineSeoulRepublic of Korea

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