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Prognostic Significance of Human Pituitary Tumor-Transforming Gene Immunohistochemical Expression in Differentiated Thyroid Cancer

Department of Pathology (C.S., C.C., M.A.J.) and Endocrinology Unit (M.A.M.-B., A.S., E.N.), Hospital Universitario Virgen del Rocío, Seville, 41013 Spain; and Department of Microbiology, Faculty of Biology, University of Seville (M.T.), and Instituto de Recursos Naturales, Consejo Superior de Investigaciones Cientificas (J.A.P.-T.), Seville 41080, Spain

Address all correspondence and requests for reprints to: Dr. Miguel A. Japón, Department of Pathology, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, Seville 41013, Spain. E-mail: mjapon{at}cica.es.

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.

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