Association between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma

Xiao Shi, Peng Cheng Yu, Bo Wen Lei, Cui Wei Li, Yan Zhang, Li Cheng Tan, Rong Liang Shi, Jie Wang, Ben Ma, Wei Bo Xu, Xiao Wang, Jia Qian Hu, Nai Si Huang, Wen Jun Wei, Yu Wang, Tong Zhen Chen, Yu Long Wang, Qing Hai Ji

Research output: Contribution to journalArticle

Abstract

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

Original languageEnglish (US)
Pages (from-to)1269-1278
Number of pages10
JournalThyroid
Volume29
Issue number9
DOIs
StatePublished - Sep 2019

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Ligands
Recurrence
CD274 Antigen
Medullary Thyroid cancer
Multivariate Analysis
Confidence Intervals
Staining and Labeling
Survival
Neoplasm Staging
Lymph Nodes
Odds Ratio
Neoplasm Metastasis
Mortality
Population

Keywords

  • biochemical recurrence/persistent disease
  • clinicopathological factor
  • medullary thyroid carcinoma
  • programmed death-ligand 1
  • structural recurrence

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Association between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma. / Shi, Xiao; Yu, Peng Cheng; Lei, Bo Wen; Li, Cui Wei; Zhang, Yan; Tan, Li Cheng; Shi, Rong Liang; Wang, Jie; Ma, Ben; Xu, Wei Bo; Wang, Xiao; Hu, Jia Qian; Huang, Nai Si; Wei, Wen Jun; Wang, Yu; Chen, Tong Zhen; Wang, Yu Long; Ji, Qing Hai.

In: Thyroid, Vol. 29, No. 9, 09.2019, p. 1269-1278.

Research output: Contribution to journalArticle

Shi, X, Yu, PC, Lei, BW, Li, CW, Zhang, Y, Tan, LC, Shi, RL, Wang, J, Ma, B, Xu, WB, Wang, X, Hu, JQ, Huang, NS, Wei, WJ, Wang, Y, Chen, TZ, Wang, YL & Ji, QH 2019, 'Association between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma', Thyroid, vol. 29, no. 9, pp. 1269-1278. https://doi.org/10.1089/thy.2019.0079
Shi, Xiao ; Yu, Peng Cheng ; Lei, Bo Wen ; Li, Cui Wei ; Zhang, Yan ; Tan, Li Cheng ; Shi, Rong Liang ; Wang, Jie ; Ma, Ben ; Xu, Wei Bo ; Wang, Xiao ; Hu, Jia Qian ; Huang, Nai Si ; Wei, Wen Jun ; Wang, Yu ; Chen, Tong Zhen ; Wang, Yu Long ; Ji, Qing Hai. / Association between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma. In: Thyroid. 2019 ; Vol. 29, No. 9. pp. 1269-1278.
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title = "Association between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma",
abstract = "Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4{\%}) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4{\%} and 57.9{\%} (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95{\%} confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40{\%}) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.",
keywords = "biochemical recurrence/persistent disease, clinicopathological factor, medullary thyroid carcinoma, programmed death-ligand 1, structural recurrence",
author = "Xiao Shi and Yu, {Peng Cheng} and Lei, {Bo Wen} and Li, {Cui Wei} and Yan Zhang and Tan, {Li Cheng} and Shi, {Rong Liang} and Jie Wang and Ben Ma and Xu, {Wei Bo} and Xiao Wang and Hu, {Jia Qian} and Huang, {Nai Si} and Wei, {Wen Jun} and Yu Wang and Chen, {Tong Zhen} and Wang, {Yu Long} and Ji, {Qing Hai}",
year = "2019",
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doi = "10.1089/thy.2019.0079",
language = "English (US)",
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TY - JOUR

T1 - Association between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma

AU - Shi, Xiao

AU - Yu, Peng Cheng

AU - Lei, Bo Wen

AU - Li, Cui Wei

AU - Zhang, Yan

AU - Tan, Li Cheng

AU - Shi, Rong Liang

AU - Wang, Jie

AU - Ma, Ben

AU - Xu, Wei Bo

AU - Wang, Xiao

AU - Hu, Jia Qian

AU - Huang, Nai Si

AU - Wei, Wen Jun

AU - Wang, Yu

AU - Chen, Tong Zhen

AU - Wang, Yu Long

AU - Ji, Qing Hai

PY - 2019/9

Y1 - 2019/9

N2 - Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

AB - Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

KW - biochemical recurrence/persistent disease

KW - clinicopathological factor

KW - medullary thyroid carcinoma

KW - programmed death-ligand 1

KW - structural recurrence

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