title: Alpha tocopherol transfer protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival.
abstract: BACKGROUND
  Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer.
  
  
  METHODS
  Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot. αΤΤP expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score.
  
  
  RESULTS
  AAPH- and BSO-induced αTTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that αTTP expression correlated with FIGO stage (p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower αTTP expression compared to cases with higher expression (p = 0.041).
  
  
  CONCLUSIONS
  The current results show that αTTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating αTTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of αTTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany. sabine.heublein@med.uni-heidelberg.de.|Department of Obstetrics and Gynecology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany. sabine.heublein@med.uni-heidelberg.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heublein
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vrekoussis
authors.affiliation: Division of Neonatology, Department of Pediatrics, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
authors.forename: Ronny
authors.initials: R
authors.lastname: Etzl
authors.affiliation: Division of Gynecologic and Perinatal Pathology, Institute of Pathology, University of Leipzig, Leipzig, Germany.|LernKlinik Leipzig, University of Leipzig, Leipzig, Germany.
authors.forename: Daisy
authors.initials: D
authors.lastname: Rotzoll
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kuhn
authors.affiliation: Department of Obstetrics and Gynecology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Faigle
authors.affiliation: Department of Obstetrics and Gynecology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Iordanis
authors.initials: I
authors.lastname: Navrozoglou
authors.affiliation: Department of Obstetrics and Gynecology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Stefos
authors.affiliation: Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Makrigiannakis
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
mesh_terms: D000578:Amidines / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D018384:Oxidative Stress / Q000502:physiology; D011379:Prognosis; D015854:Up-Regulation
chemical_list: D000578:Amidines; D002352:Carrier Proteins; C017763:alpha-tocopherol transfer protein; D019328:Buthionine Sulfoximine; C046728:2,2'-azobis(2-amidinopropane)
keywords: Alpha tocopherol transfer protein; Endometrial cancer; Survival