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

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Abstract

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.

Original languageEnglish
Pages (from-to)2983-2992
Number of pages10
JournalOncoTargets and Therapy
Volume10
DOIs
Publication statusPublished - 2017 Jun 13

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Glandular and Epithelial Neoplasms
Staining and Labeling
Tumor-Infiltrating Lymphocytes
Recurrence
Survival
Salivary Ducts
Mucoepidermoid Carcinoma
Adenoid Cystic Carcinoma
Neoplasms
Multivariate Analysis
Biomarkers
Confidence Intervals
Carcinoma
Proteins

Keywords

  • CTLA-4
  • Malignant salivary gland tumors
  • PD-L1
  • PD-L2
  • Relapse-free survival
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

@article{671e20c973494f22b34e136a6b0a7ae8,
title = "Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors",
abstract = "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 = "CTLA-4, Malignant salivary gland tumors, PD-L1, PD-L2, Relapse-free survival, Tumor-infiltrating lymphocytes",
author = "Hyeyoon Chang and Kim, {Jung Sun} and Choi, {Yoon Ji} and Jae-Gu Cho and Jeong-Soo Woo and Aeree Kim and Kim, {Jun Suk} and Kang, {Eun Joo}",
year = "2017",
month = "6",
day = "13",
doi = "10.2147/OTT.S134589",
language = "English",
volume = "10",
pages = "2983--2992",
journal = "OncoTargets and Therapy",
issn = "1178-6930",
publisher = "Dove Medical Press Ltd.",

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TY - JOUR

T1 - Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors

AU - Chang, Hyeyoon

AU - Kim, Jung Sun

AU - Choi, Yoon Ji

AU - Cho, Jae-Gu

AU - Woo, Jeong-Soo

AU - Kim, Aeree

AU - Kim, Jun Suk

AU - Kang, Eun Joo

PY - 2017/6/13

Y1 - 2017/6/13

N2 - 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.

AB - 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.

KW - CTLA-4

KW - Malignant salivary gland tumors

KW - PD-L1

KW - PD-L2

KW - Relapse-free survival

KW - Tumor-infiltrating lymphocytes

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U2 - 10.2147/OTT.S134589

DO - 10.2147/OTT.S134589

M3 - Article

VL - 10

SP - 2983

EP - 2992

JO - OncoTargets and Therapy

JF - OncoTargets and Therapy

SN - 1178-6930

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