title: Immunohistochemical features of post-radiation vaginal recurrences of endometrioid carcinomas of the endometrium: role for proteins involved in resistance to apoptosis and hypoxia.
abstract: OBJECTIVE
  Endometrioid carcinoma of the endometrium (EEC) is treated with surgery and radiotherapy. Post-radiation recurrences are associated with increased risk of metastases. Comparison of the expression of genes important in the development and progression of EEC, and others involved in resistance to apoptosis and hypoxia and adaptation to radiation, was performed between post-radiation vaginal recurrences (PVRs) and primary EECs. We tried to reproduce the results by exposing an EEC cell line to hypoxia and radiation.
  
  
  RESULTS
  Immunohistochemistry and tissue microarrays were used to compare 24 PVRs with 82 primary EECs. PVRs exhibited increased expression of p53 (P < 0.0001), cytoplasmic FLICE-inhibitory protein (FLIP) (P < 0.0001), and Ki67 (P < 0.0001), and nuclear staining for FLIP, nuclear factor kappaB (NF-κB) family members (p50, P < 0.0001; c-Rel, P = 0.0077; RelB, P = 0.0157), and β-catenin (P = 0.0001). Differences regarding p50, hypoxia-inducible factor 1α (HIF-1α), and cytoplasmic FLIP were statistically significant when PVRs and primary EECs were matched for histological grade. Exposure of the EEC cell line to hypoxia induced nuclear expression of β-catenin, FLIP, and HIF-1α, as well as increased NF-κB activity. No changes in FLIP, HIF-1α or NF-κB were seen when cells were exposed to radiation. Nuclear expression of β-catenin was seen at 3 Gy, but not at 1 Gy.
  
  
  CONCLUSIONS
  Genes involved in resistance to hypoxia are expressed in PVRs, and may play a role in the development of post-radiation recurrences.
authors.affiliation: Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Santacana
authors.forename: Andree
authors.initials: A
authors.lastname: Yeramian
authors.forename: Ana
authors.initials: A
authors.lastname: Velasco
authors.forename: Laura
authors.initials: L
authors.lastname: Bergada
authors.forename: Sonia
authors.initials: S
authors.lastname: Gatius
authors.forename: Virginia
authors.initials: V
authors.lastname: García
authors.forename: Ainara
authors.initials: A
authors.lastname: Azueta
authors.forename: Jose
authors.initials: J
authors.lastname: Palacios
authors.forename: Xavier
authors.initials: X
authors.lastname: Dolcet
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D019394:Ki-67 Antigen / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011832:Radiation Injuries / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D046888:Tissue Array Analysis; D014625:Vaginal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C495270:CTNNB1 protein, human; D019394:Ki-67 Antigen; D016328:NF-kappa B; D009363:Neoplasm Proteins; D051176:beta Catenin