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This version published online on January 17, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2532
A more recent version of this article appeared on April 1, 2006
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Submitted on November 21, 2005
Accepted on January 5, 2006

Prognostic Significance of hPTTG Immunohistochemical Expression in Differentiated Thyroid Cancer

Carmen Sáez, M. Asunción Martínez-Brocca, Carolina Castilla, Alfonso Soto, Elena Navarro, María Tortolero, José A. Pintor-Toro, and Miguel A. Japón*

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; Department of Microbiology [M. T.], Faculty of Biology, University of Seville, Seville, 41080 Spain; and Instituto de Recursos Naturales [J. A. P.-T.], CSIC, Seville, 41080 Spain

* To whom correspondence should be addressed. E-mail: mjapon{at}cica.es.

Context: Human securin hPTTG is over-expressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC).

Objective: 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. Median follow-up of 43 months allowed us to analyze persistence of disease and 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 (BNTD, n = 35).

Intervention: None.

Main Outcome Measure: Association between hPTTG expression and prognostic factors in DTC.

Results: Among DTC cases, 21 (35%) showed low and 39 (65%) high hPTTG immunostaining. Adjacent non-neoplastic thyroid tissue was largely unstained. Among BNTD cases, immunostaining was detected focally in 8 (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). Significant association with TNM was also found, as 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). Association between hPTTG over-expression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as independent prognostic factor for persistent disease (RR 3.0; 95% CI 1.1-8.7; P < 0.05).

Conclusions: Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.


Key words: Differentiated Thyroid Cancer • Pituitary Tumor-Transforming Gene • Prognostic Significance • Immunohistochemistry




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