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PMID: 27086918 Published · ppublish English Comparative Study Journal Article

Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants.

Oncotarget ·Vol. 7 ·No. 22 ·2016-05-31 ·Pages 32318-28

Chowdhury S, Veyhl J, Jessa F, Polyakova O, Alenzi A, MacMillan C, Ralhan R, Walfish PG

Abstract

Programmed death-ligand 1(PD-L1) expression on tumor cells is emerging as a potential predictive biomarker in anti-PD-L1 directed cancer immunotherapy. We analyzed PD-L1 expression in papillary thyroid carcinoma (PTC) and its variants and determined its prognostic potential to predict clinical outcome in these patients. This study was conducted at an academic oncology hospital which is a prime referral centre for thyroid diseases. Immunohistochemical subcellular localization (IHC) analyses of PD-L1 protein was retrospectively performed on 251 archived formalin fixed and paraffin embedded (FFPE) surgical tissues (66 benign thyroid nodules and 185 PTCs) using a rabbit monoclonal anti-PD-L1 antibody (E1L3N, Cell Signaling Technology) and detected using VECTASTAIN rapid protocol with diaminobenzidine (DAB) as the chromogen. The clinical-pathological factors and disease outcome over 190 months were assessed; immunohistochemical subcellular localization of PD-L1 was correlated with disease free survival (DFS) using Kaplan Meier survival and Cox multivariate regression analysis. Increased PD-L1 immunostaining was predominantly localized in cytoplasm and occasionally in plasma membrane of tumor cells. Among all combined stages of PTC, patients with increased PD-L1 membrane or cytoplasmic positivity had significantly shorter median DFS (36 months and 49 months respectively) as compared to those with PD-L1 negative tumors (DFS, both 186 months with p < 0.001 and p < 0.01 respectively). Comparison of PD-L1+ and PD-L1- patients with matched staging showed increased cytoplasmic positivity in all four stages of PTC that correlated with a greater risk of recurrence and a poor prognosis, but increased membrane positivity significantly correlated with a greater risk of metastasis or death only in Stage IV patients. In conclusion, PD-L1 positive expression in PTC correlates with a greater risk of recurrence and shortened disease free survival supporting its potential application as a prognostic marker for PTC.

Keywords
benign nodule programmed death-ligand 1 protein biomarkers subcellular localization thyroid cancer
MeSH Terms
Adolescent Adult Aged Aged, 80 and over B7-H1 Antigen/analysis Biomarkers, Tumor/analysis Carcinoma, Papillary/chemistry,mortality,secondary,therapy Chi-Square Distribution Disease Progression Disease-Free Survival Female Goiter, Nodular/metabolism,pathology Humans Immunohistochemistry Kaplan-Meier Estimate Male Middle Aged Multivariate Analysis Neoplasm Recurrence, Local Neoplasm Staging Ontario Predictive Value of Tests Proportional Hazards Models Retrospective Studies Risk Factors Thyroid Cancer, Papillary Thyroid Neoplasms/chemistry,mortality,pathology,therapy Time Factors Treatment Outcome Young Adult
Chemicals
B7-H1 Antigen Biomarkers, Tumor CD274 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Chowdhury Subrata
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
Veyhl Joe
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
Jessa Fatima
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
Polyakova Olena
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada.
Alenzi Ahmed
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada.
MacMillan Christina
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. | Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Ralhan Ranju
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada. | Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada. | Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Walfish Paul G
Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada. | Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. | Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada. | Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Conflict of Interest

PGW and RR are shareholders in Proteocyte Diagnostics Inc. All the other authors (SC, JV, FJ, OP, AA and CM) have nothing to disclose.

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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.8698
Published
2016-05-31
Pages
32318-28
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC5078015
Subset
IM
External Links
PubMed source DOI: 10.18632/oncotarget.8698 PMC Full Text View journal details
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