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Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors

Authors Chang H, Kim JS, Choi YJ, Cho J, Woo J, Kim A, Kim JS, Kang EJ

Received 14 February 2017

Accepted for publication 19 April 2017

Published 13 June 2017 Volume 2017:10 Pages 2983—2992

DOI https://doi.org/10.2147/OTT.S134589

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Carlos Vigil Gonzales

Hyeyoon Chang,1 Jung Sun Kim,2 Yoon Ji Choi,3 Jae-Gu Cho,4 Jeong-Soo Woo,4 Aeree Kim,1 Jun Suk Kim,5 Eun Joo Kang5

1Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 2Division of Oncology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Seoul, Korea; 3Division of Oncology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea; 4Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 5Division of Oncology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea

Objectives: PD-1/PD-L1 and CTLA-4 have been investigated and are thought to play an important role in tumor evasion. This study aimed to investigate expression patterns of immune-related molecules, and their clinical impacts in malignant salivary gland tumors.
Patients and methods: We performed immunohistochemical staining for PD-L1, PD-L2, CTLA-4, PD-1, and CD8+ tumor-infiltrating lymphocytes in 70 malignant salivary gland tumors. Protein expression was assessed by H-score by multiplying the staining intensity by the percentage of cells with positive staining.
Results: The tumors comprised mucoepidermoid carcinomas (38.6%), adenoid cystic carcinomas (21.4%), salivary duct carcinomas (15.7%), and others. In malignant salivary gland tumors, PD-L2 expression was high, while expression of PD-L1 was relatively low in terms of the percentage of positively stained cells and the staining intensity. In univariate analysis, PD-L2 expression (H-score <1 vs ≥1), PD-1 (H-score <1 vs ≥1), and CD8+ tumor-infiltrating lymphocytes (H-score <1 vs ≥1) were significant prognostic factors. In multivariate analysis, low PD-L2 expression (H-score <1) was independently associated with shorter relapse-free survival (hazard ratio =6.514; 95% confidence interval, 1.2–36.2; P=0.032).
Conclusion: In summary, PD-L2 is potentially an important biomarker in malignant salivary gland tumors, especially in regard to relapse.

Keywords: malignant salivary gland tumors, PD-L1, PD-L2, CTLA-4, tumor-infiltrating lymphocytes, relapse-free survival
 

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