PMID- 31616183
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220410
IS  - 1179-1322 (Print)
IS  - 1179-1322 (Electronic)
IS  - 1179-1322 (Linking)
VI  - 11
DP  - 2019
TI  - Correlation of NRF2 and progesterone receptor and its effects on ovarian cancer 
      biology.
PG  - 7673-7684
LID - 10.2147/CMAR.S210004 [doi]
AB  - PURPOSE: This study aimed to investigate the potential prognostic impact of 
      nuclear factor erythroid 2-related factor 2 (NRF2) and progesterone receptor A 
      (PRA)/progesterone receptor B (PRB) in ovarian cancer patients which might be the 
      rationale for putative new treatment strategies. PATIENTS AND METHODS: The 
      presence of NRF2 and PRA/PRB was investigated in 156 ovarian cancer samples using 
      immunohistochemistry (IHC). Staining of NRF2 and PRA/PRB was rated using the 
      semi-quantitative immunoreactive score (IR score, Remmele's score) and correlated 
      to clinical and pathological data. NRF2 and PRA/PRB expression were compared with 
      respect to the overall survival (OS). RESULTS: NRF2 staining was different in 
      both, the cytoplasm and nucleus between the histological subtypes (p=0.001 and 
      p=0.02, respectively). There was a significant difference in the PRA expression 
      comparing all histological subtypes (p=0.02). Histological subtypes showed no 
      significant differences in the PRB expression. A strong correlation of 
      cytoplasmic NRF2 and PRA expression was detected (cc=0.247, p=0.003) as well as 
      of cytoplasmic NRF2 and PRB expression (cc=0.25, p=0.003), confirmed by 
      immunofluorescence double staining. Cytoplasmic NRF2 expression was associated 
      with a longer OS (median 50.6 vs 32.5 months; p=0.1) as it was seen for PRA 
      expression (median 63.4 vs 33.1 months; p=0.08), although not statistically 
      significant. In addition, high PRB expression (median 80.4 vs 32.5 months; 
      p=0.04) and concurrent expression of cytoplasmic NRF2 and PRA were associated 
      with a significantly longer OS (median 109.7 vs 30.6 months; p=0.02). The same 
      relationship was also noted for NRF2 and PRB with improved OS for patients 
      expressing both cytoplasmic NRF2 and PRB (median 153.5 vs 30.6 months; p=0.009). 
      Silencing of NFE2L2 induced higher mRNA expression of PGR in the cancer cell line 
      OVCAR3 (p>0.05) confirming genetic interactions of NRF2 and PR. CONCLUSION: In 
      this study, the combination of cytoplasmic NRF2 and high PRA/PRB expression was 
      demonstrated to be associated with improved overall survival in ovarian cancer 
      patients. Further understanding of interactions within the NRF2/AKR1C1/PR pathway 
      could open new additional therapeutic approaches.
CI  - (c) 2019 Czogalla et al.
FAU - Czogalla, Bastian
AU  - Czogalla B
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Kahaly, Maja
AU  - Kahaly M
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Mayr, Doris
AU  - Mayr D
AD  - Faculty of Medicine, Institute of Pathology, Lmu Munich, Munich, Germany.
FAU - Schmoeckel, Elisa
AU  - Schmoeckel E
AD  - Faculty of Medicine, Institute of Pathology, Lmu Munich, Munich, Germany.
FAU - Niesler, Beate
AU  - Niesler B
AD  - Department of Human Molecular Genetics, Institute of Human Genetics, University 
      of Heidelberg, Heidelberg, Germany.
FAU - Hester, Anna
AU  - Hester A
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Zeder-Goss, Christine
AU  - Zeder-Goss C
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Kolben, Thomas
AU  - Kolben T
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Burges, Alexander
AU  - Burges A
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Mahner, Sven
AU  - Mahner S
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Jeschke, Udo
AU  - Jeschke U
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
FAU - Trillsch, Fabian
AU  - Trillsch F
AD  - Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20190814
PL  - New Zealand
TA  - Cancer Manag Res
JT  - Cancer management and research
JID - 101512700
PMC - PMC6699153
OTO - NOTNLM
OT  - immunohistochemistry
OT  - nuclear factor erythroid 2-related factor 2
OT  - ovarian cancer
OT  - progesterone receptor
COIS- Bastian Czogalla has received a research grant from the "Monika Kutzner" 
      foundation and "Brigitte & Dr. Konstanze Wegener" foundation. Anna Hester has 
      received a research grant from the "Walter Schulz" foundation and advisory board, 
      speech honoraria and travel expenses from Roche and Pfizer. Thomas Kolben s 
      relative is employed at Roche AG. Research support, advisory board, honoraria, 
      and travel expenses from AstraZeneca, Clovis, Medac, MSD, Novartis, PharmaMar, 
      Roche, Sensor Kinesis, Tesaro, Teva have been received by Sven Mahner and from 
      AstraZeneca, Medac, PharmaMar, Roche, Tesaro by Fabian Trillsch. All authors 
      report no other conflicts of interest in this work.
EDAT- 2019/10/17 06:00
MHDA- 2019/10/17 06:01
PMCR- 2019/08/14
CRDT- 2019/10/17 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/06/27 00:00 [accepted]
PHST- 2019/10/17 06:00 [entrez]
PHST- 2019/10/17 06:00 [pubmed]
PHST- 2019/10/17 06:01 [medline]
PHST- 2019/08/14 00:00 [pmc-release]
AID - 210004 [pii]
AID - 10.2147/CMAR.S210004 [doi]
PST - epublish
SO  - Cancer Manag Res. 2019 Aug 14;11:7673-7684. doi: 10.2147/CMAR.S210004. 
      eCollection 2019.