Significance of chromogranin A and synaptophysin in medullary thyroid carcinomas

Medullary thyroid carcinoma (MTC) is a rare thyroid carcinoma of C-cell deviation that produces and secretes calcitonin (CT) and chromogranin A (CgA) into the blood. Thus, CT and CgA are immunohistochemical and serum markers for MTCs. MTC occurs in sporadic and inheritable forms. The hallmark of inheritable cases in multiple endocrine neoplasm 2 (MEN2) is MTC. MEN2 cases represent 30% through germline RET proto-oncogene mutation and occur in younger ages involving bilateral thyroid lobes. Sporadic cases are 70% and occur in older ages. CgA and synaptophysin (SPY) are the two most widely used and reliable immunohistochemical markers for neuroendocrine tumors, including MTCs. This study aimed to detect different immunohistochemical staining patterns for CgA and SPY between non-symptomatic small lesions and invading larger aggressive tumors in both MEA2 cases and sporadic cases. There was different CgA and SPY immunostaining in MEA2 cases where small tumors (≤0.3 cm) were lesser immunostained for CgA and SPY, despite intense staining for CT, compared to the larger (≥0.5 cm) tumors, stronger immunostained for CgA. There was also different CgA and SPY immunohistochemical staining in sporadic cases between small lesions (≤0.5 cm) and larger tumors (≥1.0 cm). One small sporadic tumor (0.5 cm × 0.3 cm) was strongly and weakly, patchy stained for CgA and SPY, respectively, while larger sporadic tumors were diffusely and strongly stained for CgA and SPY. Therefore, stronger CgA and SPY immunostaining for larger tumors in both MEA2 and sporadic cases may be used as independent, aggressive immunohistochemical markers for MTCs.