Immunohistochemical Subcellular Localization of Protein Biomarkers Distinguishes Benign from Malignant Thyroid Nodules: Potential for Fine-Needle Aspiration Biopsy Clinical Application
| Autor: | Ajitha Jeganathan, Paul G. Walfish, Akram Alyass, Christina MacMillan, Jeremy L. Freeman, Joe Veyhl, Raj Thani Somasundaram, Ian J. Witterick, Jasmeet Assi, Ranju Ralhan, Seham Chaker, Allan Vescan |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Thyroid nodules Pathology medicine.medical_specialty Endocrinology Diabetes and Metabolism Biopsy Fine-Needle Thyroid Gland Proteomics Malignancy Sensitivity and Specificity Diagnosis Differential Thyroid carcinoma Young Adult Endocrinology Biopsy medicine Humans Thyroid Neoplasms Thyroid Nodule Aged Retrospective Studies Aged 80 and over medicine.diagnostic_test business.industry Middle Aged medicine.disease Immunohistochemistry Carcinoma Papillary Fine-needle aspiration Biomarker (medicine) Female business Biomarkers Subcellular Fractions |
| Zdroj: | Thyroid. 25:1224-1234 |
| ISSN: | 1557-9077 1050-7256 |
| DOI: | 10.1089/thy.2015.0114 |
| Popis: | 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).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.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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|