Antonia Wenners1, Felix Hartmann2, Arne Jochens3, Anna Maria Roemer2, Ibrahim Alkatout2, Wolfram Klapper4, Marion van Mackelenbergh2, Christoph Mundhenke2, Walter Jonat2, Maret Bauer2. 1. Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany. antonia.wenners@gmx.de. 2. Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3, 24105, Kiel, Germany. 3. Institute for Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Brunswiker Straße 10, 24105, Kiel, Germany. 4. Institute of Pathology, University Medical Center Schleswig-Holstein, Arnold-Heller-Str. 3/14, 24105, Kiel, Germany.
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. CONCLUSION: 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.
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 humanbreast cancer. They are involved in intratumoral progesterone metabolism. METHODS: Immunohistochemistry was performed on tissue microarrays from 504 core biopsies from breast cancerpatients. 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. CONCLUSION: 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 cancerpatients, independent of classic hormone receptor status.
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