Elevated expression of the tyrosine phosphatase SHP-1 defines a subset of high-grade breast tumors.
OBJECTIVE
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.
Insabato
Luigi
L
Biomorphological and Functional Science, Anatomic Pathology Section, Faculty of Medicine, Università degli Studi di Napoli Federico II, Napoli, Italia.
Amelio
Ivano
I
Quarto
Maria
M
Zannetti
Antonella
A
Tolino
Fabio
F
de Mauro
Gaia
G
Cerchia
Laura
L
Riccio
Patrizia
P
Baumhoer
Daniel
D
Condorelli
Gerolama
G
Terracciano
Luigi
L
de Franciscis
Vittorio
V
D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D007150:Immunohistochemistry; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000032:analysis*
D019941:Cyclin-Dependent Kinase Inhibitor p16; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6