Systematic Review and Meta-Analysis to Identify the Immunocytochemical Markers Effective in Delineating Benign from Malignant Thyroid Lesions in FNAC Samples

Uma Mohan; Sumsum P Sunny; Pramila Mendonca; Moni A Kuriakose; Subramanian Kannan; Amritha Suresh

doi:10.1007/s12022-022-09721-5

Systematic Review and Meta-Analysis to Identify the Immunocytochemical Markers Effective in Delineating Benign from Malignant Thyroid Lesions in FNAC Samples

Endocr Pathol. 2022 Jun;33(2):243-256. doi: 10.1007/s12022-022-09721-5. Epub 2022 May 21.

Authors

Uma Mohan^{1

2}, Sumsum P Sunny^{1

2}, Pramila Mendonca^{1

2}, Moni A Kuriakose^{1

2}, Subramanian Kannan³, Amritha Suresh⁴

Affiliations

¹ Department of Head and Neck Oncology, Mazumdar Shaw Medical Center, NH Health City, Bangalore, India.
² Integrated Head and Neck Oncology Program, DSRG-5, Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India.
³ Department of Endocrinology, Mazumdar Shaw Medical Center, NH Health City, Bangalore, India.
⁴ Integrated Head and Neck Oncology Program, DSRG-5, Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India. amritha.suresh@ms-mf.org.

PMID: 35596875
DOI: 10.1007/s12022-022-09721-5

Abstract

Conventional cytology-based diagnosis for thyroid cancer is limited with more than 30-45% of nodules categorized as indeterminate, necessitating surgery for confirming or refuting the diagnosis. This systematic review and meta-analysis were aimed at identifying immunocytochemical markers effective in delineating benign from malignant thyroid lesions in fine needle aspiration cytology (FNAC) samples, thereby improving the accuracy of cytology diagnosis. A systematic review of relevant articles (2000-2021) from online databases was carried out and the search protocol registered in PROSPERO database (CRD42021229121). The quality of studies was assessed using QUADAS-2. Review Manager 5.4.1 from Cochrane collaboration and MetaDisc Version 1.4 was used to conduct the meta-analysis. Bias in the studies were visually analyzed using funnel plots, and statistical significance was evaluated by Egger's test. Systematic review identified 64 original articles, while meta-analysis in eligible articles (n = 41) identified a panel of 5 markers, Galectin-3, HBME-1, CK-19, CD-56, and TPO. Assessment of the diagnostic performance revealed that Gal-3 (sensitivity: 0.81; CI: 0.79-0.83; specificity: 0.84; CI: 0.82-0.85) and HBME-1 (sensitivity: 0.83; Cl: 0.81-0.86; specificity: 0.85; CI: 0.83-0.86) showed high accuracy in delineating benign from malignant thyroid nodules. Efficacy analysis in indeterminate nodules showed Gal-3 and HBME-1 have high specificity of 0.86 (CI 0.84-0.89) and 0.82 (CI 0.78-0.86), respectively, and low sensitivity of 0.76 (CI 0.72-0.80) and 0.75 (CI 0.70-0.80), respectively. Diagnostic odds ratio (DOR) of Galectin-3 and HBME-1 were 39.18 (CI 23.38-65.65) and 24.44 (CI 11.16-53.54), respectively. Significant publication bias was observed for the markers Galectin-3 and CK-19 (p < 0.05). The panel of 5 markers identified from this meta-analysis are high-confidence candidates that need to be validated in thyroid cytology to establish their efficacy and enable clinical applicability.

Keywords: Galectin-3; HBME-1; Immunocytochemistry; Meta-analysis; Systematic review; Thyroid.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Biomarkers, Tumor / analysis
Biopsy, Fine-Needle / methods
Galectin 3 / analysis
Humans
Sensitivity and Specificity
Thyroid Neoplasms* / diagnosis
Thyroid Neoplasms* / pathology
Thyroid Nodule* / diagnosis
Thyroid Nodule* / pathology

Substances

Biomarkers, Tumor
Galectin 3