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

J Clin Endocrinol Metab. 2006 Apr;91(4):1404-9. doi: 10.1210/jc.2005-2532. Epub 2006 Jan 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology
  • Aged
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Goiter, Nodular / genetics
  • Goiter, Nodular / metabolism
  • Goiter, Nodular / pathology
  • Humans
  • Immunohistochemistry
  • Iodides / metabolism
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Paraffin Embedding
  • Prognosis
  • Proportional Hazards Models
  • Securin
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*

Substances

  • Iodides
  • Neoplasm Proteins
  • Securin
  • pituitary tumor-transforming protein 1, human