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Overexpression of Urinary Plasminogen Activator (uPA) Protein and mRNA in Thyroid Carcinogenesis

Chu, Quyen D MD*; Hurd, Thelma C MD*; Harvey, Shashi PHD*; Martinick, Maisie BS*; Markus, Gabor MD, PHD‡; Tan, Dongfeng MD†; Gibbs, John F MD*; Loree, Thom MD*

Diagnostic Molecular Pathology: December 2004 - Volume 13 - Issue 4 - pp 241-246
Original Article
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Objective: Urinary plasminogen activator (uPA), a protease, is one of the critical components of tumor invasion and metastasis. Its expression in thyroid carcinoma and potential role in thyroid tumorigenesis are unknown. The objective of this study was to determine whether uPA is differentially expressed in benign and malignant thyroid tumors.

Design: uPA expression was evaluated by immunohistochemistry (IHC) in 20 thyroid tumors (six classic papillary thyroid cancers (PTC) and three tall cell variants (TCV) and 11 adenomas). To validate IHC results, in situ hybridization was performed on both adenomas and cancer tissues to explore the expression of uPA at the mRNA level. The Fisher exact test was used to compare protein as well as mRNA expressions in adenomas and thyroid cancer.

Results: Intense granular cytoplasmic staining for uPA was observed in five of nine (56%) of thyroid cancers: 2/6 classic PTC (33%) and all tall cell variant PTC. Furthermore, uPA mRNA expression was found in the malignant thyroid epithelium but not in adjacent normal thyroid follicles or the stromal elements. None of the adenomas expressed uPA (P = .008). uPA staining was absent in histologically normal follicles adjacent to malignant thyroid follicles.

Conclusions: uPA is expressed in thyroid carcinoma but not in benign adenomas or normal adjacent follicles. The selective expression of uPA in thyroid carcinoma provides evidence that uPA is useful in distinguishing benign and malignant thyroid neoplasms. More importantly, uPA may represent molecular target for therapeutic treatment of this malignancy.

From the *Department of Surgical Oncology, †Department of Pathology, and ‡Department of Biochemistry, Roswell Park Cancer Institute, State University of New York at Buffalo, Buffalo, New York.

Supported, in part, by Roswell Alliance Foundation Grant 862-2083 (to S.R.H.) and by shared resources of the Roswell Park Cancer Center Support Grant NIH CA 16056.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Reprints: Shashi Harvey, PhD, Division of Surgical Oncology, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263 (e-mail: shashi.harvey@roswellpark.org).

© 2004 Lippincott Williams & Wilkins, Inc.