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Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants.
Oncotarget. 2016 May 31; 7(22):32318-28.O

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.

Authors+Show Affiliations

Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.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.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.Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.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.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.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27086918

Citation

Chowdhury, Subrata, et al. "Programmed Death-ligand 1 Overexpression Is a Prognostic Marker for Aggressive Papillary Thyroid Cancer and Its Variants." Oncotarget, vol. 7, no. 22, 2016, pp. 32318-28.
Chowdhury S, Veyhl J, Jessa F, et al. Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants. Oncotarget. 2016;7(22):32318-28.
Chowdhury, S., Veyhl, J., Jessa, F., Polyakova, O., Alenzi, A., MacMillan, C., Ralhan, R., & Walfish, P. G. (2016). Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants. Oncotarget, 7(22), 32318-28. https://doi.org/10.18632/oncotarget.8698
Chowdhury S, et al. Programmed Death-ligand 1 Overexpression Is a Prognostic Marker for Aggressive Papillary Thyroid Cancer and Its Variants. Oncotarget. 2016 May 31;7(22):32318-28. PubMed PMID: 27086918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants. AU - Chowdhury,Subrata, AU - Veyhl,Joe, AU - Jessa,Fatima, AU - Polyakova,Olena, AU - Alenzi,Ahmed, AU - MacMillan,Christina, AU - Ralhan,Ranju, AU - Walfish,Paul G, PY - 2016/03/23/received PY - 2016/03/26/accepted PY - 2016/4/19/entrez PY - 2016/4/19/pubmed PY - 2017/12/27/medline KW - benign nodule KW - programmed death-ligand 1 KW - protein biomarkers KW - subcellular localization KW - thyroid cancer SP - 32318 EP - 28 JF - Oncotarget JO - Oncotarget VL - 7 IS - 22 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27086918/Programmed_death_ligand_1_overexpression_is_a_prognostic_marker_for_aggressive_papillary_thyroid_cancer_and_its_variants_ L2 - https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.8698 DB - PRIME DP - Unbound Medicine ER -