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Elevated Expression of the Tyrosine Phosphatase SHP-1 Defines a Subset of High-Grade Breast Tumors

Insabato L.a · Amelio I.d · Quarto M.b · Zannetti A.e · Tolino F.d · de Mauro G.d · Cerchia L.d · Riccio P.c · Baumhoer D.f · Condorelli G.c · Terracciano L.f · de Franciscis V.d
aBiomorphological and Functional Science, Anatomic Pathology Section, Faculty of Medicine, bDipartimento Scienze Fisiche, cDipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, dIstituto di Endocrinologia ed Oncologia Sperimentale, e eIstituto di Biostrutture e Bioimmagini, CNR, Napoli, Italia; fInstitute of Pathology, University Hospital, Basel, Switzerland Oncology 2009;77:378–384 (DOI:10.1159/000276765)

Abstract

Objectives: Protein tyrosine phosphatases are key regulators of intracellular signaling that contribute to determining cancer cell growth, which thus makes them attractive targets for therapeutic and diagnostic agents. SHP-1 phosphotyrosine phosphatase is rarely expressed in epithelial tumor cells, but expression has been found in several breast cancer cell lines and tumors. To determine the potential significance of SHP-1 as a prognostic marker in the clinical setting, we examined SHP-1 protein expression in breast tumors. Methods: We analyzed SHP-1 expression by immunohistochemistry in a breast tissue microarray composed of 2,081 cores, either alone or in combination with known prognostic markers. Results: Our data showed that SHP-1 expression was confined to a well-defined subset of high-grade tumors characterized by unique biological parameters. SHP-1 expression correlated directly with expression of the tyrosine kinase receptor HER-2 and inversely with expression of the estrogen receptor, while it was weakly associated with Bcl-2 expression. Conclusions: Levels of SHP-1 were correlated with conventional pathologic parameters of tumor aggressiveness and were associated with reduced patient survival, suggesting that elevated expression of SHP-1 is a common molecular abnormality in a defined subset of breast tumors and might be used in routine diagnosis to identify patients with high-risk tumors.

 

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