High expression of obesity-linked phosphatase SHIP2 in invasive breast cancer correlates with reduced disease-free survival

Tumour Biol. 2008;29(5):330-41. doi: 10.1159/000172970. Epub 2008 Nov 15.

Abstract

SH2-containing 5'-inositol phosphatase (SHIP2) is a known regulator of insulin function. Genetic knockout of SHIP2 in mice causes mild insulin hypersensitivity and prevents high-fat-diet-induced obesity. SHIP2 also regulates actin remodeling and epidermal growth factor receptor (EGFR) turnover and supports breast cancer; and metastatic growth. To determine the clinical significance of SHIP2 expression in breast cancer and its relationship to relevant oncogenic molecules, SHIP2 expression was determined immunohistochemically in 285 primary breast cancers; 140 ductal carcinomas in situ (DCIS) and 145 invasive carcinomas. Forty-five percent of the specimens showed high SHIP2 levels in cancer cells while only 15% of adjacent normal cells expressed high SHIP2 levels (p < 0.0001). In cancer cells, the risk of SHIP2 overexpression is elevated (a) in women aged < or =50 years (relative risk, RR = 4.13; 95% confidence interval, CI, 2.5-6.9) compared to women aged >50 years (RR = 2.37; 95% CI 1.6-3.5; p = 0.0003), and (b) in invasive carcinomas (RR = 3.52; 95% CI 2.3-5.5) compared with DCIS (RR = 2.22; 95% CI 1.5-3.5; p = 0.0009). Patients with higher SHIP2 levels in invasive carcinomas had significantly reduced disease-free (p = 0.0025) and overall survival periods (p = 0.0228). In invasive carcinomas, SHIP2 correlated with estrogen receptor absence (p = 0.003) and EGFR presence (p = 0.0147). In conclusion, SHIP2 is an important biomarker for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Intraductal, Noninfiltrating / metabolism*
  • Carcinoma, Intraductal, Noninfiltrating / mortality
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Case-Control Studies
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / metabolism*
  • Prognosis
  • Survival Rate
  • src Homology Domains

Substances

  • Biomarkers, Tumor
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases