Ranju Ralhan1,2,3,4,5,6, Joe Veyhl1, Seham Chaker1, Jasmeet Assi1, Akram Alyass1, Ajitha Jeganathan1, Raj Thani Somasundaram1, Christina MacMillan2,3, Jeremy Freeman4,5,6, Allan D Vescan4,5,6, Ian J Witterick4,5,6, Paul G Walfish1,2,3,4,7,8. 1. 1 Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital , Toronto, Canada . 2. 2 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital , Toronto, Canada . 3. 3 Laboratory Medicine and Pathobiology, University of Toronto , Toronto, Canada . 4. 4 Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital , Toronto, Canada . 5. 5 Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital , Toronto, Canada . 6. 6 Department of Otolaryngology-Head and Neck Surgery, University of Toronto , Toronto, Canada . 7. 7 Department of Medicine, Endocrine Division, Mount Sinai Hospital , Toronto, Canada . 8. 8 Department of Medicine, University of Toronto Medical School , Toronto, Canada .
Abstract
BACKGROUND: It is of critical clinical importance to select accurately for surgery thyroid nodules at risk for malignancy and avoid surgery on those that are benign. Using alterations in subcellular localization for seven putative biomarker proteins (identified by proteomics), this study aimed to define a specific combination of proteins in surgical tissues that could distinguish benign from malignant nodules to assist in future surgical selection by fine-needle aspiration biopsy (FNAB). METHODS: Immunohistochemical subcellular localization (IHC) analyses of seven proteins were retrospectively performed on surgical tissues (115 benign nodules and 114 papillary-based thyroid carcinomas [TC]), and a risk model biomarker panel was developed and validated. The biomarker panel efficacy was verified in 50 FNAB formalin-fixed and paraffin-embedded cell blocks, and 26 cytosmears were prepared from fresh surgically resected thyroid nodules. RESULTS: Selection modeling using these proteins resulted in nuclear phosphoglycerate kinase 1 (PGK1) loss and nuclear Galectin-3 overexpression as the best combination for distinguishing TC from benign nodules (area under the curve [AUC] 0.96 and 0.95 in test and validation sets, respectively). A computed malignancy score also accurately identified TC in benign and indeterminate nodules (test and validation sets: AUC 0.94, 0.90; specificity 98%, 99%). Its efficacy was confirmed in surgical FNAB cell blocks and cytosmears. CONCLUSION: Using surgical tissues, it was observed that a combination of PGK1 and Galectin-3 had high efficiency for distinguishing benign from malignant thyroid nodules and could improve surgical selection for TC among indeterminate nodules. Further validation in prospective preoperative FNAB will be required to confirm such a clinical application.
BACKGROUND: It is of critical clinical importance to select accurately for surgery thyroid nodules at risk for malignancy and avoid surgery on those that are benign. Using alterations in subcellular localization for seven putative biomarker proteins (identified by proteomics), this study aimed to define a specific combination of proteins in surgical tissues that could distinguish benign from malignant nodules to assist in future surgical selection by fine-needle aspiration biopsy (FNAB). METHODS: Immunohistochemical subcellular localization (IHC) analyses of seven proteins were retrospectively performed on surgical tissues (115 benign nodules and 114 papillary-based thyroid carcinomas [TC]), and a risk model biomarker panel was developed and validated. The biomarker panel efficacy was verified in 50 FNAB formalin-fixed and paraffin-embedded cell blocks, and 26 cytosmears were prepared from fresh surgically resected thyroid nodules. RESULTS: Selection modeling using these proteins resulted in nuclear phosphoglycerate kinase 1 (PGK1) loss and nuclear Galectin-3 overexpression as the best combination for distinguishing TC from benign nodules (area under the curve [AUC] 0.96 and 0.95 in test and validation sets, respectively). A computed malignancy score also accurately identified TC in benign and indeterminate nodules (test and validation sets: AUC 0.94, 0.90; specificity 98%, 99%). Its efficacy was confirmed in surgical FNAB cell blocks and cytosmears. CONCLUSION: Using surgical tissues, it was observed that a combination of PGK1 and Galectin-3 had high efficiency for distinguishing benign from malignant thyroid nodules and could improve surgical selection for TC among indeterminate nodules. Further validation in prospective preoperative FNAB will be required to confirm such a clinical application.
Authors: Anne M-Y Hsieh; Olena Polyakova; Guodong Fu; Ronald S Chazen; Christina MacMillan; Ian J Witterick; Ranju Ralhan; Paul G Walfish Journal: Oncotarget Date: 2018-04-13