title: Insulin growth factor receptor-1 expression and loss of PTEN protein predict early recurrence in triple-negative breast cancer.
abstract: OBJECTIVE
  Insulin-like growth factor receptor-1 (IGFR-1) and its signalling axis promote tumorigenesis, metastasis, and resistance to existing forms of cancer therapy, and have become a major focus for the development of anticancer drugs. As oncological management options for triple-negative breast cancers (TNBCs) are limited, there is potential for the rapid development of novel selective anticancer agents specifically targeting components of the PTEN-phosphoinositide 3-kinase-AKT pathway, including the phosphorylated form of AKT (pAKT) and the tumour suppressor molecule PTEN. The aim of this study was to conduct immunohistochemical analyses to examine the levels of PTEN, IGFR-1 and pAKT expression in TNBCs, and determine whether these levels correlated with poor prognosis in this subset of aggressive breast cancers.
  
  
  RESULTS
  Immunohistochemistry was performed on paraffin-embedded tumour tissues from a consecutive cohort of 144 female patients diagnosed with TNBC. Associations of IGFR-1, PTEN and pAKT expression with clinicopathological parameters, disease-free survival (DFS) and overall survival (OS) were evaluated. There were significant increases in IGFR-1 expression (99%) and pAKT expression (92%) with concomitant loss of PTEN expression in the majority of cases (63%). Increased IGFR-1 expression and loss of PTEN expression were associated with reduced OS and DFS, respectively. pAKT expression showed a strong correlation with basal-like expression. Combinatorial immunophenotypic analyses showed that loss of PTEN expression with concomitant IGFR-1 expression correlated with poor DFS.
  
  
  CONCLUSIONS
  A high percentage of PTEN loss with overexpression of IGFR-1 and pAKT in TNBC indicates the potential of these molecules for predicting early recurrence and/or as targets in the formulation of effective alternative therapy regimens.
authors: Department of Pathology, Singapore General Hospital, SingaporeDepartment of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
authors: Jabed
authors: J
authors: Iqbal
authors: Aye Aye
authors: AA
authors: Thike
authors: Poh Yian
authors: PY
authors: Cheok
authors: Gary Man-Kit
authors: GM
authors: Tse
authors: Puay Hoon
authors: PH
authors: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human