title: Stromal markers AKR1C1 and AKR1C2 are prognostic factors in primary human breast cancer.
abstract: BACKGROUND
  Stromal fibroblasts influence tumor growth and progression. We evaluated two aldo-keto reductases, AKR1C1 and AKR1C2, in stromal fibroblasts and carcinoma cells as prognostic factors in primary human breast cancer. They are involved in intratumoral progesterone metabolism.
  
  
  METHODS
  Immunohistochemistry was performed on tissue microarrays from 504 core biopsies from breast cancer patients. Primary endpoints were disease-free (DFS) and overall (OS) survival.
  
  
  RESULTS
  AKR1C1 and AKR1C2 expression in fibroblasts and tumor cells correlated with favorable tumor characteristics, such as small tumor size and negative nodal status. In univariate analysis, AKR1C1 expression in carcinoma cells correlated positively with DFS und OS; AKR1C2 expression in both fibroblasts and tumor cells also showed a positive correlation with DFS and OS. In multivariate analysis, AKR1C1 expression in carcinoma cells was an independent prognostic marker.
  
  
  CONCLUSIONS
  It can be assumed that our observations are due to the independent regulatory function of AKR1C1/2 in progesterone metabolism and therefore provide a basis for new hormone-based therapy options for breast cancer patients, independent of classic hormone receptor status.
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany. antonia.wenners@gmx.de.
authors.forename: Antonia
authors.initials: A
authors.lastname: Wenners
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Hartmann
authors.affiliation: Institute for Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Brunswiker Straße 10, 24105, Kiel, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Jochens
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Roemer
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Alkatout
authors.affiliation: Institute of Pathology, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3/14, 24105, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: van Mackelenbergh
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mundhenke
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Jonat
authors.affiliation: Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
authors.forename: Maret
authors.initials: M
authors.lastname: Bauer
mesh_terms: D015089:20-Hydroxysteroid Dehydrogenases / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D002277:Carcinoma / Q000737:chemistry* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000737:chemistry*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis*; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D047368:Tumor Burden; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D015089:20-Hydroxysteroid Dehydrogenases; D015415:Biomarkers; D006913:Hydroxysteroid Dehydrogenases; C115140:3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
keywords: AKR1C1; AKR1C2; Primary breast cancer; Prognostic factors; Stromal markers; Tumor microenvironment