Survivin and Fas Ligand Expressions Are Correlated with Angiolymphatic Tumor Spread in Medullary Thyroid Carcinoma

ABSTRACT

BACKGROUND: Medullary thyroid carcinoma (MTC) that originates from C cells comprises about 10% of all the malignant thyroid tumors. Activating mutations of the RET proto-oncogene have been found to be involved in the anti-apoptotic pathway of MTC that harbors the RET mutation. We investigated the correlation between the clinicopathologic parameters and the expressions of survivin, a novel anti-apoptotic molecule, and the other apoptosis-related proteins, and the known prognostic markers. METHODS: Immunohistochemical staining was performed using antibodies for survivin, Fas, Fas ligand (FasL), bcl-2, calcitonin, CEA and cyclin A in 19 case of MTC; 10 sporadic MTCs, eight multiple endocrine neoplasia (MEN) type 2A MTCs and one familial MTC (FMTC). RESULTS: Survivin protein expression was found in five cases (26%) and this was correlated with the presence of angiolymphatic tumor emboli (p=0.019). FasL was expressed in 14 cases (74%) and it had correlation with the presence of lymph node metastases (p=0.029). The cyclin A-labeling indices were correlated with local invasiveness (p=0.001). CONCLUSIONS: Survivin and FasL might be involved in the lymphatic tumor spread of MTC.