title: Src homology phosphotyrosyl phosphatase-2 expression is an independent negative prognostic factor in human breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland. muensts@uhbs.ch
authors.forename: Simone
authors.initials: S
authors.lastname: Muenst
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Obermann
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Viehl
authors.forename: Walter P
authors.initials: WP
authors.lastname: Weber
authors.forename: Timothy
authors.initials: T
authors.lastname: Fleming
authors.forename: William E
authors.initials: WE
authors.lastname: Gillanders
authors.forename: Savas D
authors.initials: SD
authors.lastname: Soysal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*
chemical_list: D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11