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

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.