TROP-2 AND THE HISTOMORPHOLOGICAL SPECTRUM OF THYROID LESIONS

Abstract

Background: Thyroid lesions encompass a broad histomorphological spectrum, ranging from benign lesions to low-risk neoplasms and various malignant neoplasms, with considerable morphological overlap among certain entities. TROP-2, a transmembrane glycoprotein implicated in tumour progression, has demonstrated variable expression in thyroid neoplasms. Evaluation of its immunoexpression across different histomorphological patterns may provide insights into its relationship with the morphological spectrum of thyroid lesions. Aim: To evaluate the pattern and intensity of TROP-2 immunoexpression across the histomorphological spectrum of thyroid lesions and to assess the differences in its expression among various thyroid lesion categories and histological subtypes. Materials and Methods: Our prospective observational study included 44 surgically resected thyroid specimens representing a spectrum of histomorphologically distinct thyroid lesions. Histopathological examination was performed to classify the lesions based on their morphological features. TROP-2 IHC was assessed by evaluating membranous staining intensity and H-score. Cases were categorized as benign (n=16), low-risk thyroid neoplasms (n=6), and malignant lesions (n=22). The pattern and degree of TROP-2 expression were compared across the different histomorphological categories and histological subtypes. Statistical analyses were performed to determine the association between TROP-2 expression and the histomorphological spectrum of thyroid lesions. Results: TROP-2 immunoexpression showed a progressive increase across benign, low-risk, and malignant thyroid lesions. Benign lesions demonstrated minimal expression, with positivity in only 1 of 17 cases (5.9%) and a mean H-score of 11.76 ± 48.51. Low-risk lesions showed limited and heterogeneous expression, with positivity in 33.3% of cases and a mean H-score of 25.83 ± 46.32. Malignant lesions demonstrated markedly higher expression, with positivity in 77.3% of cases and a mean H-score of 137.27 ± 113.73. A statistically significant association was observed between TROP-2 expression and lesion category (p < 0.001). Conclusion: TROP-2 immunoexpression varies across the histomorphological spectrum of thyroid lesions, with minimal expression in benign lesions and substantially higher expression in malignant lesions, particularly PTC and its variants. The heterogeneous expression observed among different histological subtypes highlights the variable relationship between TROP-2 and thyroid tumour morphology. These findings suggest that TROP-2 may serve as a useful adjunctive immunohistochemical marker for characterizing thyroid lesions across a diverse histomorphological spectrum.