AIMS: Src homology phosphotyrosyl phosphatase-2 (SHP2) is a ubiquitously expressed phosphatase that plays an essential role in the downstream signalling pathways of multiple growth factor receptors, thus representing a potential target for cancer therapy. Recent studies suggest that SHP2 contributes to tumour initiation, progression and metastasis in breast cancer, yet the impact of SHP2 expression on prognosis in human breast cancer has not been evaluated. METHODS AND RESULTS: To explore further the role of SHP2 in breast cancer, we conducted an immunohistochemical study using a tissue microarray encompassing 1401 formalin-fixed breast cancer specimens with detailed clinical annotation and outcome data. Of 1401 evaluable breast cancers, 651 (46%) were positive for SHP2. SHP2 expression was associated positively with tumour grade, lymph node status and tumour stage. In univariate survival analysis, cases with SHP2 expression had a significantly worse overall survival (OS). In multivariate analysis, SHP2 remained an independent negative prognostic factor for OS. SHP2 expression was a negative prognostic factor for OS in the luminal A and the luminal B HER2(-) intrinsic subtypes. CONCLUSIONS: Our data demonstrate for the first time that SHP2 is an independent predictor of survival in breast cancer, suggesting that SHP2 may be a potential target for therapy.
AIMS: Src homology phosphotyrosyl phosphatase-2 (SHP2) is a ubiquitously expressed phosphatase that plays an essential role in the downstream signalling pathways of multiple growth factor receptors, thus representing a potential target for cancer therapy. Recent studies suggest that SHP2 contributes to tumour initiation, progression and metastasis in breast cancer, yet the impact of SHP2 expression on prognosis in humanbreast cancer has not been evaluated. METHODS AND RESULTS: To explore further the role of SHP2 in breast cancer, we conducted an immunohistochemical study using a tissue microarray encompassing 1401 formalin-fixed breast cancer specimens with detailed clinical annotation and outcome data. Of 1401 evaluable breast cancers, 651 (46%) were positive for SHP2. SHP2 expression was associated positively with tumour grade, lymph node status and tumour stage. In univariate survival analysis, cases with SHP2 expression had a significantly worse overall survival (OS). In multivariate analysis, SHP2 remained an independent negative prognostic factor for OS. SHP2 expression was a negative prognostic factor for OS in the luminal A and the luminal B HER2(-) intrinsic subtypes. CONCLUSIONS: Our data demonstrate for the first time that SHP2 is an independent predictor of survival in breast cancer, suggesting that SHP2 may be a potential target for therapy.
Authors: Mohamed Bentires-Alj; Susana G Gil; Richard Chan; Zhigang C Wang; Yongping Wang; Naoko Imanaka; Lyndsay N Harris; Andrea Richardson; Benjamin G Neel; Haihua Gu Journal: Nat Med Date: 2005-12-20 Impact factor: 53.440
Authors: Mohamed Bentires-Alj; J Guillermo Paez; Frank S David; Heike Keilhack; Balazs Halmos; Katsuhiko Naoki; John M Maris; Andrea Richardson; Alberto Bardelli; David J Sugarbaker; William G Richards; Jinyan Du; Luc Girard; John D Minna; Mignon L Loh; David E Fisher; Victor E Velculescu; Bert Vogelstein; Matthew Meyerson; William R Sellers; Benjamin G Neel Journal: Cancer Res Date: 2004-12-15 Impact factor: 12.701
Authors: M Bocanegra; A Bergamaschi; Y H Kim; M A Miller; A B Rajput; J Kao; A Langerød; W Han; D-Y Noh; S S Jeffrey; D G Huntsman; A-L Børresen-Dale; J R Pollack Journal: Oncogene Date: 2009-11-02 Impact factor: 9.867