Simple SummaryThyroid nodules are very common as one gets older. Fine-needle aspiration is the primary diagnostic methodology but difficulties in the diagnosis of follicular-derived thyroid lesions are well-known. The aim of this study was to assess the potential of G-protein coupled receptor-associated sorting protein 1 (GASP-1) as a valid thyroid cancer biomarker. By using anti-GASP-1 polyclonal antibodies in immunohistochemical (IHC) staining studies, we found that GASP-1 was significantly overexpressed in early-stage malignant thyroid neoplasms while it was minimally expressed in normal thyroid cells. We demonstrated that the level of GASP-1 expression can differentiate follicular adenoma from follicular carcinoma.AbstractFollicular neoplasms are classified as benign or malignant depending on the presence or absence of capsular and/or vascular invasion. Due to incomplete capsular penetration or equivocal vascular invasion, the evaluation of these features can be challenging using histologic examination. In the current study, we analyzed the involvement of G-protein coupled receptor-associated sorting protein 1 (GASP-1) in the development and progression of thyroid neoplasms. Affinity-purified anti-GASP-1 polyclonal antibodies were used for routine immunohistochemistry (IHC) analysis. Thyroid tissue microarrays containing normal thyroid tissue, follicular adenoma, follicular carcinoma, papillary thyroid carcinoma, and anaplastic carcinoma were analyzed. We found that the level of GASP-1 expression can differentiate follicular adenoma from follicular carcinoma. When numerous cases were scored for GASP-1 expression by a board-certified pathologist, we found that GASP-1 expression is 7-fold higher in thyroid malignant neoplasms compared to normal thyroid tissue, and about 4-fold higher in follicular carcinoma compared to follicular adenoma. In follicular adenoma tissues, we observed the presence of many mini-glands that are enriched in GASP-1 and some mini-glands contain as few as three cells. GASP-1 IHC also possesses several advantages over the conventional H&E and can be used to identify early thyroid cancer and monitor cancer progression.