Research Papers:

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

Subrata Chowdhury, Joe Veyhl, Fatima Jessa, Olena Polyakova, Ahmed Alenzi, Christina MacMillan, Ranju Ralhan and Paul G. Walfish _

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Oncotarget. 2016; 7:32318-32328. https://doi.org/10.18632/oncotarget.8698

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Subrata Chowdhury1, Joe Veyhl1, Fatima Jessa1, Olena Polyakova1,7, Ahmed Alenzi1,7, Christina MacMillan3,4, Ranju Ralhan1,2,3,4,5,6, Paul G. Walfish1,2,3,4,7

1Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada

2Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada

3Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

4Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

5Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada

6Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada

7Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada

Correspondence to:

Paul G. Walfish, email: [email protected]

Ranju Ralhan, email: [email protected]

Keywords: thyroid cancer, benign nodule, programmed death-ligand 1, protein biomarkers, subcellular localization

Received: March 23, 2016     Accepted: March 26, 2016     Published: April 12, 2016


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.

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