Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer

Context: Human securin pituitary tumor-transforming gene ( hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). Objective: The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. Design: hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. Setting: The study was conducted at a tertiary university hospital. Patients: Ninety-five patients undergoing surgical resection for DTC ( n = 60) or benign nodular thyroid disease ( n = 35) were studied. Main Outcome Measure: The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. Results: Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal ( P < 0.01) or distant metastases ( P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG ( P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant ( P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease ( relative risk, 3.0; 95% confidence interval, 1.1 - 8.7; P < 0.05). Conclusions: Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.