title: Progesterone receptor negativity is an independent risk factor for relapse in patients with early stage endometrioid endometrial adenocarcinoma.
abstract: OBJECTIVE
  In endometrioid endometrial adenocarcinoma (EEA), the currently established prognostic factors in clinical guidelines are stage and grade. Many guidelines include lymphovascular invasion (LVI) and tumor size as prognostic factors. Although several studies have associated lack of estrogen (ER) and progesterone receptor (PR) expression with reduced outcome, the prognostic use of these markers is uncommon. Better prognostication of clinical behavior would be useful in patients with early stage (I-II) disease. In this study we evaluated ER and PR as prognostic factors in EEA, and compared their expression with other potential biomarkers and clinical parameters.
  
  
  METHODS
  Tissue microarrays were constructed from 182 patients with stages I-II EEA. ER, PR, p53, Ki-67, PTEN, MLH and HER-2 expression were assessed by immunohistochemical staining and HER-2 was confirmed with SISH. The results were correlated with clinicopathologic parameters and to disease-free survival.
  
  
  RESULTS
  Eleven patients (6%) developed recurrent disease during a median follow up time of 62.8 months. In univariate analysis FIGO grade (p=0.019), positive expression of p53 (p=0.010) and negative PR expression (p=0.001) were associated with a shorter disease-free survival. In multivariate analysis only negative PR expression (p=0.019) was significantly associated with a shorter disease-free survival. LVI and tumor size where not of prognostic value.
  
  
  CONCLUSIONS
  Lack of PR expression is a strong, independent risk factor for tumor recurrence in patients with stages I-II endometrioid endometrial cancer. The use of this easily measurable biomarker as a prognostic factor in the clinical context should be considered and tested in a larger patient population.
authors.affiliation: Department of Pathology, University of Turku, Turku, Finland. jutta.huvila@utu.fi
authors.forename: Jutta
authors.initials: J
authors.lastname: Huvila
authors.forename: Lauri
authors.initials: L
authors.lastname: Talve
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Edqvist
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.forename: Seija
authors.initials: S
authors.lastname: Grénman
authors.forename: Annika
authors.initials: A
authors.lastname: Auranen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000556:secondary* / Q000628:therapy; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*; D012307:Risk Factors; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C501486:MLH1 protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human
keywords: Biomarker; Endometrial cancer; Progesterone receptor; Prognostic factor