TY - JOUR
T1 - Expression of programmed death-1 in sentinel lymph nodes of breast cancer
AU - Tatara, Takashi
AU - Mukohara, Toru
AU - Shimono, Yohei
AU - Yamasaki, Takashi
AU - Imamura, Yoshinori
AU - Funakoshi, Yohei
AU - Toyoda, Masanori
AU - Kiyota, Naomi
AU - Takao, Shintaro
AU - Kono, Seishi
AU - Kakeji, Yoshihiro
AU - Minami, Hironobu
N1 - Funding Information:
Grant-in-Aid for Scientific Research (C), Grant number: 15K08588; Novartis Pharma Research Grants; Research Grant from the Takeda Science Foundation
Funding Information:
We thank Ms. Emmy Yanagita and staff members of the Kobe University Hospital Advanced Tissue Staining Center (KATS) for their excellent technical support in immunohistochemistry. We thank Edanz Group (www.edanzediting.com) for editing a draft of this manuscript. This study was supported by the Grant-in-Aid for Scientific Research (C) (T.M.) (15K08588), Research Grant from the Takeda Science Foundation (T.M), and Novartis Pharma Research Grants (T.M.).
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Background and Objectives: To explore whether lymphocytes in sentinel lymph nodes (SLNs) are highly exposed to tumor neoantigens and thus express high level of programmed death 1 (PD-1), we examined PD-1 expression in SLNs and non-sentinel regional lymph nodes (non-SLNs) in breast cancer. Methods: We performed PD-1 immunohistochemistry in two cohorts: 40 metastasis-negative SLNs including 10 patients for each subtype (luminal A-like, luminal B-like, HER2, and triple negative breast cancer [TNBC]); and 25 pairs of metastasis-positive SLNs and non-SLNs (10 luminal A-like, 10 luminal B-like, and 5 TNBC). Results: Among 40 metastasis-negative SLNs, 34 and 6 samples were PD-1 intensity grade 1 (low) and 2 (high), respectively. PD-1 intensity correlated with PD-1-positive lymphocyte numbers (P = 0.005); TNBC had the highest PD-1 lymphocyte numbers among all subtypes. The median PD-1-positive lymphocyte number was higher in SLNs than non-SLNs. In most cases, more lymphocytes in SLNs expressed PD-1 than those in non-SLNs (P < 0.0001). Conclusions: TNBC had the greatest PD-1 expression among all subtypes, and metastasis-positive SLNs had more PD-1-positive lymphocytes than downstream non-SLNs. These data suggested that lymphocytes in SLNs are activated following exposure to tumor neoantigens and thus tumor specific, and could be utilized as a biomarker platform.
AB - Background and Objectives: To explore whether lymphocytes in sentinel lymph nodes (SLNs) are highly exposed to tumor neoantigens and thus express high level of programmed death 1 (PD-1), we examined PD-1 expression in SLNs and non-sentinel regional lymph nodes (non-SLNs) in breast cancer. Methods: We performed PD-1 immunohistochemistry in two cohorts: 40 metastasis-negative SLNs including 10 patients for each subtype (luminal A-like, luminal B-like, HER2, and triple negative breast cancer [TNBC]); and 25 pairs of metastasis-positive SLNs and non-SLNs (10 luminal A-like, 10 luminal B-like, and 5 TNBC). Results: Among 40 metastasis-negative SLNs, 34 and 6 samples were PD-1 intensity grade 1 (low) and 2 (high), respectively. PD-1 intensity correlated with PD-1-positive lymphocyte numbers (P = 0.005); TNBC had the highest PD-1 lymphocyte numbers among all subtypes. The median PD-1-positive lymphocyte number was higher in SLNs than non-SLNs. In most cases, more lymphocytes in SLNs expressed PD-1 than those in non-SLNs (P < 0.0001). Conclusions: TNBC had the greatest PD-1 expression among all subtypes, and metastasis-positive SLNs had more PD-1-positive lymphocytes than downstream non-SLNs. These data suggested that lymphocytes in SLNs are activated following exposure to tumor neoantigens and thus tumor specific, and could be utilized as a biomarker platform.
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U2 - 10.1002/jso.24937
DO - 10.1002/jso.24937
M3 - Article
C2 - 29193094
AN - SCOPUS:85036501204
VL - 117
SP - 1131
EP - 1136
JO - Journal of Surgical Oncology
JF - Journal of Surgical Oncology
SN - 0022-4790
IS - 6
ER -