Role of GDF-15 as an Immunohistochemical Marker in Follicular Neoplasms and Lesions of Thyroid

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Published Jun 26, 2023
DOI: https://doi.org/10.18103/mra.v11i6.4036

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Main Article Content

Neelaiah Siddaraju, MD
Senior Professor, Department of Pathology Jawaharlal Institute of Medical Education and Research (JIPMER) Puducherry-605006, INDIA
Prasanna Venkadesa Perumal, B.Sc. (MLT), M.Sc. (MLT-Cytopathology)
Laboratory Technician, Department of Microbiology Jawaharlal Institute of Medical Education and Research (JIPMER) Puducherry-605006, INDIA
Sunil Kumar Saxena, MS
Professor, Department of Otorhinolaryngology Jawaharlal Institute of Medical Education and Research (JIPMER) Puducherry-605006, INDIA
Soundravally Rajendiran, MD
Professor, Department of Biochemistry Jawaharlal Institute of Medical Education and Research (JIPMER) Puducherry-605006, INDIA
Ramachandra V. Bhat, MD
Dean & Professor of Pathology Indira Gandhi Medical College and Research Institute (IGMC &RI) Puducherry-605006, INDIA

Abstract

Introduction: A pre-therapeutic distinction between benign and malignant thyroid nodules is critical for deciding the therapeutic strategy, wherein fine-needle aspiration cytology plays a major role. However, there are grey-zone categories in the Bethesda system for reporting thyroid cytopathology, which is currently, the universally accepted pattern for reporting thyroid FNAC. Several immunomarkers studied in these ‘indeterminate’ lesions have proven to be of limited value. Recent molecular studies have shown the growth differentiation factor-15 (GDF-15) gene to be a promising marker in various malignancies; though, there is sparse literature regarding its use as a surrogate immunohistochemical marker, especially in thyroid neoplasms. The present (pilot) study explores its possible utility in the pre-therapeutic distinction of follicular-patterned lesions and neoplasms of the thyroid by testing it initially on histopathologic sections.
Objective: To assess the utility of GDF-15 as an immunohistochemical marker in distinguishing common follicular-patterned thyroid neoplasms and lesions.
Materials and Methods: GDF-15 immunohistochemistry was performed on 75 surgical specimens of thyroid lesions, comprising 19 adenomatous nodules or follicular hyperplasias, 10 nodular goitres, 17 follicular thyroid adenomas, 8 follicular thyroid carcinomas, 12 follicular variant of papillary thyroid carcinomas, and 9 conventional papillary thyroid carcinomas. All these cases were histologically proven, and their immunohistochemical interpretation was performed using the immunoreactive scoring system. Pearson’s analysis was performed for the immunohistochemical correlation among the study groups.
Results: The findings were inconsistent; 16 follicular-patterned malignancies (5 follicular carcinomas and 11 cases of follicular variant of papillary carcinoma) and seven conventional papillary thyroid carcinomas revealed both cytoplasmic and membranous expression of GDF-15. All benign lesions were negative except one follicular adenoma and three follicular hyperplasias, which exhibited patchy or focal GDF-15 positivity. However, three follicular carcinomas, one follicular variant of papillary carcinoma, and two conventional papillary carcinomas were found to be GDF-15-negative.
Conclusion: Though there is a literature backup supporting the use of GDF-15 gene analysis in differentiating various follicular-patterned neoplasms, the GDF-15 protein, as an immunohistochemical marker failed to distinguish not only between benign and malignant follicular-patterned neoplasms but also between follicular carcinoma and follicular variant of papillary carcinoma.

Keywords: thyroid, GDF-15, immunohistochemistry, follicular neoplasm, follicular adenoma, follicular carcinoma, follicular hyperplasia, follicular variant of papillary carcinoma

Article Details

How to Cite
SIDDARAJU, Neelaiah et al. Role of GDF-15 as an Immunohistochemical Marker in Follicular Neoplasms and Lesions of Thyroid. Medical Research Archives, [S.l.], v. 11, n. 6, june 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4036>. Date accessed: 21 nov. 2024. doi: https://doi.org/10.18103/mra.v11i6.4036.
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Issue
Vol 11 No 6 (2023): June Issue, Vol.11, Issue 6
Section
Research Articles

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References

1. Vanderpump M. The epidemiology of thyroid disease. Br Med Bull. 2011;99:39-51. doi:10.1093/bmb/ldr030.
2. Unnikrishnan A, Menon U. Thyroid disorders in India: an epidemiological perspective. Indian J Endocrinol Metab. 2011;15:78. doi:10.4103/2230-8210.83329.
3. Subasree S. Prevalence of thyroid disorders in India: an overview. Research J of Pharm and Tech. 2014;7:1165–8. doi: 10.5958/0974- 360X.
4. DeMay R. Follicular lesions of the thyroid. Am J Clin Pathol. 2000;114:681-3. doi:10.1309/bul2-7v05-dgxu-hu6e.
5. Chan J. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002;117:16-8. doi:10.1309/p7ql-16kq-qlf4- xw0m.
6. Cerilli L, Mills S, Rumpel C, Dudley T, Moskaluk C. Interpretation of RET immunostaining in follicular lesions of the thyroid. Am J Clin Pathol. 2002;118:186-93. doi:10.1309/53uc- 4u88-rrtn-h33g.
7. Bose D, Das R, Chatterjee U, Banerjee U. Cytokeratin 19 immunoreactivity in the diagnosis of papillary thyroid carcinoma. Indian J. Med. Paediatr. Oncol. 2012;33:107- 11. doi:10.4103/0971-5851.99746.
8. Weber F, Shen L, Aldred M, Morrison C, Frilling A, et al. Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination.J. Clin. Endocrinol. Metab. 2005;90:2512-21. doi:10.1210/jc.2004-2028.
9. Saleh H, Jin B, Barnwell J, Alzohaili O. Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules. Diagn Pathol. 2010;5. doi:10.1186/1746-1596-5-9.
10. Liu H, Lin F. Application of immunohistochemistry in thyroid pathology. Arch. Pathol. Lab. Med. 2015;139:67-82. doi:10.5858/arpa.2014-0056-ra.
11. Kang Y, Kim J, Lim M, Lee S, Yi S, et al. Growth differentiation factor 15 is a cancer cell-induced mitokine that primes thyroid cancer cells for invasiveness. Thyroid. 2021;31: 772-786. doi:10.1089/thy.2020.0034.
12. Vaňhara P, Hampl A, Kozubík A, Souček K. Growth/differentiation factor-15: prostate cancers suppressor or promoter? Prostate Cancer Prostatic Dis. 2012;15:320-8. doi:10.1038/pcan.2012.6.
13. Tamhane S, Gharib H. Thyroid nodule update on diagnosis and management. Clin Diabetes Endocrinol. 2016;2:17.doi:10.1186/s40842- 016-0035-7.
14. Wallin U, Glimelius B, Jirström K, Darmanis S,Nong R, et al. Growth differentiation factor 15: a prognostic marker for recurrence in colorectal cancer. Br J Cancer. 2011;104:1619-27. doi:10.1038/bjc.2011.112.
15. Peake B, Eze S, Yang L, Castellino R, Nahta R. Growth differentiation factor 15 mediates epithelial-mesenchymal transition and invasion of breast cancers through IGF-1R-FoxM1 signaling. Oncotarget. 2017; 8:94393-406. doi:10.18632/oncotarget.21765.
16. Liu X, Chi X, Gong Q, Gao L,Niu Y, et al. Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma. PLoS One. 2015;10:e0127518. doi: 10.1371/journal.pone.012751.
17. Zhang, H, Zhang W, Tu X, Niu Y, Li X, et al. Elevated serum growth differentiation factor 15 levels are associated with thyroid nodules in type 2 diabetes aged over 60 years. Oncotarget, 8, pp. 41379– 41386. https://doi.org/10.18632/oncotarget.17328.
18. Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis result in the bone tissue-a review. Diagn Pathol. 2014:9.doi:10.1186/s13000-014-0221-9.
19. Poller DN, Glaysher S. Molecular pathology and thyroid FNA. Cytopathology. 2017;28:475-523. doi: 10.1111/cyt.12492.
20. Ni Z, Wang Y, Peng S, Yuan Z. Expression of growth differentiation factor 15 in papillary thyroid carcinoma and its clinical significance. Cancer Research and Clinic. 2021;6:282–6.ID: wpr-886049.
21. Joo M, Kim D, Lee M, Lee H, Kim J. GDF15 promotes cell growth, migration, and invasion in gastric cancer by inducing STAT3 activation. Int J Mol Sci. 2023;24. doi:10.3390/ijms24032925.
22. Rochette L, Méloux A, Zeller M, Cottin Y, Vergely C. Functional roles of GDF-15 in modulating microenvironment to promote carcinogenesis. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165798. doi:10.1016/j.bbadis.2020.165798.
23. Prabakaran I, Grau J, Lewis R, Fraker D, Guvakova M. Rap2AIs upregulated in invasive cells dissected from follicular thyroid cancer. J Thyroid Res. 2011;2011:1-6.
doi: 10.4061/2011/979840.