title: PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors.
abstract: OBJECTIVE
  Clonal loss of PTEN expression occurs frequently in endometrial carcinoma and endometrial hyperplasia. Limited data from immunohistochemical studies suggest that PTEN-null appearing endometrial glands are detectable in women without pathologic abnormalities, but the relationship of PTEN expression to endometrial cancer risk factors has not been extensively explored. We evaluated relationships between endometrial cancer risk factors and loss of PTEN expression in a set of benign endometrial samples prospectively collected from women undergoing hysterectomy and in endometrial cancer tissues from a population-based case-control study.
  
  
  METHODS
  We used a validated PTEN immunohistochemical assay to assess expression in epidemiological studies designed to assess benign endometrium [Benign Reproductive Tissue Evaluation Study (n = 73); Einstein Endometrium Study (n = 19)], and endometrial cancer [Polish Endometrial Cancer Study (n = 148)] tissues. Associations between endometrial cancer risk factors (collected via study-specific risk factor questionnaires) and PTEN expression in endometrial tissues were determined using Fisher's exact tests.
  
  
  RESULTS
  PTEN loss was detected in 19% of benign endometrial tissues versus 55% in endometrial cancers. NSAID use was statistically significantly associated with PTEN loss in the benign endometrium (p = 0.02).
  
  
  CONCLUSIONS
  Our data demonstrate that PTEN loss is detectable in endometrial tissues that are benign and malignant, with substantially more frequent loss in endometrial cancer compared with benign endometrium. However, alterations in expression were unrelated to most risk factors in this analysis, except for the association with NSAID use, which may represent a chance finding or reverse causality among patients with endometriosis who may have PTEN pathway abnormalities in eutopic endometrium. Further evaluation of factors associated with PTEN loss and long-term follow-up of women with PTEN-null endometrial glands may be useful in understanding early events in endometrial carcinogenesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room #7E238, Bethesda, MD, 20892-9774, USA. yanghan@mail.nih.gov.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Yang
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Meeker
authors.affiliation: Magee Women's Hospital of the UPMC System, Pittsburgh, PA, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Guido
authors.affiliation: Imperial College London, London, UK.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Obstetrics and Gynecology and Women's Health; and Molecular Pharmacology, Albert Einstein Cancer Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Gloria S
authors.initials: GS
authors.lastname: Huang
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room #7E238, Bethesda, MD, 20892-9774, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Luhn
authors.affiliation: Magee Women's Hospital of the UPMC System, Pittsburgh, PA, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: d'Ambrosio
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room #7E238, Bethesda, MD, 20892-9774, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room #7E238, Bethesda, MD, 20892-9774, USA.|Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D012307:Risk Factors
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Endometrial cancer; PTEN; Risk factors