title: High PTEN gene expression is a negative prognostic marker in human primary breast cancers with preserved p53 function.
abstract: OBJECTIVE
  PTEN is an important tumor suppressor in breast cancer. Here, we examined the prognostic and predictive value of PTEN and PTEN pseudogene (PTENP1) gene expression in patients with locally advanced breast cancer given neoadjuvant chemotherapy.
  
  
  METHODS
  The association between pretreatment PTEN and PTENP1 gene expression, response to neoadjuvant chemotherapy, and recurrence-free and disease-specific survival was assessed in 364 patients with locally advanced breast cancer given doxorubicin, 5-fluorouracil/mitomycin, or epirubicin versus paclitaxel in three phase II prospective studies. Further, protein expression of PTEN or phosphorylated Akt, S6 kinase, and 4EBP1 was assessed in a subgroup of 187 tumors.
  
  
  RESULTS
  Neither PTEN nor PTENP1 gene expression level predicted response to any of the chemotherapy regimens tested (n = 317). Among patients without distant metastases (n = 282), a high pretreatment PTEN mRNA level was associated with inferior relapse-free (RFS; p = 0.001) and disease-specific survival (DSS; p = 0.003). Notably, this association was limited to patients harboring TP53 wild-type tumors (RFS; p = 0.003, DSS; p = 0.009). PTEN mRNA correlated significantly with PTENP1 mRNA levels (rs= 0.456, p < 0.0001) and PTEN protein staining (rs= 0.163, p = 0.036). However, no correlation between PTEN, phosphorylated Akt, S6 kinase or 4EBP1 protein staining, and survival was recorded. Similarly, no correlation between PTENP1 gene expression and survival outcome was observed.
  
  
  CONCLUSIONS
  High intratumoral PTEN gene expression was associated with poor prognosis in patients with locally advanced breast cancers harboring wild-type TP53.
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Synnøve
authors.initials: S
authors.lastname: Yndestad
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Eilin
authors.initials: E
authors.lastname: Austreid
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Section of Molecular Pathology, Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Chrisanthar
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.|The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Peer Kåre
authors.initials: PK
authors.lastname: Lilleng
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway. hans.eikesdal@k2.uib.no.|Department of Oncology, Haukeland University Hospital, Bergen, Norway. hans.eikesdal@k2.uib.no.
authors.forename: Hans Petter
authors.initials: HP
authors.lastname: Eikesdal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Locally advanced breast cancer; PTEN; Predictive factors; Prognosis; p53