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

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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.

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Acknowledgements

The authors duly acknowledge institutional support provided by Mazumdar Shaw Medical Foundation (MSMF).

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Authors and Affiliations

  1. Department of Head and Neck Oncology, Mazumdar Shaw Medical Center, NH Health City, Bangalore, India

    Uma Mohan, Sumsum P. Sunny, Pramila Mendonca & Moni A. Kuriakose

  2. Integrated Head and Neck Oncology Program, DSRG-5, Mazumdar Shaw Center for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India

    Uma Mohan, Sumsum P. Sunny, Pramila Mendonca, Moni A. Kuriakose & Amritha Suresh

  3. Department of Endocrinology, Mazumdar Shaw Medical Center, NH Health City, Bangalore, India

    Subramanian Kannan

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Contributions

All the authors UM, SS, PM, AS, SK, and MK contributed to the development of study concept and design. UM and PM independently searched the database and collected the data. Data analysis was carried out by UM and SS.. The first draft of the manuscript was written by UM, reviewed, and commented by AS, SK, and MK. The final manuscript was read and approved by all authors.

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Correspondence to Amritha Suresh.

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12022_2022_9721_MOESM1_ESM.tif

Supplementary file1: Funnel plot of markers in differentiating benign from malignant thyroid nodules in FNAC samples (a) Galectin-3, (b) HBME-1, (c) CK-19, (d) CD56, (e) TPO (TIF 609 KB)

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Supplementary file2: Funnel plot of markers after sensitivity analysis in differentiating benign from malignant thyroid nodules in FNAC samples (a) Galectin-3, (b) HBME-1, (c) CK-19 (TIF 527 KB)

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Supplementary file3: SROC curve of markers after sensitivity analysis in differentiating benign from malignant thyroid nodules in FNAC samples (a) Galectin-3, (b) HBME-1, (c) CK-19 (TIF 710 KB)

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Supplementary file4: Pooled specificity of markers in differentiating benign from malignant thyroid nodules in FNAC samples (a) Galectin-3, (b) HBME-1, (c) CK-19, (d) CD56, (e) TPO (TIF 2201 KB)

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Supplementary file5: Pooled sensitivity of markers in differentiating benign from malignant thyroid nodules in FNAC samples (a) Galectin-3, (b) HBME-1, (c) CK-19, (d) CD56, (e) TPO (TIF 2133 KB)

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Supplementary file6: Descriptive Forest plot showing DOR after sensitivity analysis of markers (a) Galectin-3, (b) HBME-1, (c) CK-19 in differentiating benign from malignant thyroid nodules in FNAC samples (TIF 1461 KB)

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Supplementary file7: SROC curve of (a) Galectin-3 and (b) HBME-1 in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 638 KB)

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Supplementary file8: Descriptive Forest plot showing DOR after sensitivity analysis of(a) Galectin-3 and (b) HBME-1 in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 1241 KB)

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Supplementary file9: SROC curve of (a) Galectin-3 and (b) HBME-1 after sensitivity analysis in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 639 KB)

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Supplementary file10: Pooled sensitivity of (a) Galectin-3 and (b) HBME-1 in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 1030 KB)

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Supplementary file11: Pooled specificity of (a) Galectin-3 and (b) HBME-1 in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 1030 KB)

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Supplementary file12: Funnel plot of (a) Galectin-3 and (b) HBME-1 in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 476 KB)

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Supplementary file13: Funnel plot after sensitivity analysis of (a) Galectin-3 and (b) HBME-1in delineating indeterminate category of thyroid nodules in FNAC samples (TIF 489 KB)

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Supplementary file19 (PDF 133 KB)

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Mohan, U., Sunny, S.P., Mendonca, P. et al. Systematic Review and Meta-Analysis to Identify the Immunocytochemical Markers Effective in Delineating Benign from Malignant Thyroid Lesions in FNAC Samples. Endocr Pathol 33, 243–256 (2022). https://doi.org/10.1007/s12022-022-09721-5

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