Article open access publication

Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study

British Journal of Cancer, Springer Nature, ISSN 0007-0920

Volume 111, 12, 2014

DOI:10.1038/bjc.2014.567, Dimensions: pub.1013142192, PMC: PMC4264456, PMID: 25349970,

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  1. (1) University of Calgary, grid.22072.35
  2. (2) Melanoma Institute Australia, University of Sydney, Royal Prince Alfred Hospital, Gloucester House–level 3, Missenden Road, 2050, Camperdown, NSW, Australia
  3. (3) University of British Columbia, grid.17091.3e
  4. (4) University of Southern California, grid.42505.36
  5. (5) University of Toronto, grid.17063.33
  6. (6) University of Cambridge, grid.5335.0
  7. (7) Queen's Medical Centre, grid.415598.4
  8. (8) University of Melbourne, grid.1008.9
  9. (9) Peter MacCallum Cancer Centre, grid.1055.1
  10. (10) Roswell Park Cancer Institute, grid.240614.5
  11. (11) University College London, grid.83440.3b
  12. (12) Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054, Erlangen, Germany
  13. (13) Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Krankenhausstrasse 8-10, 91054, Erlangen, Germany
  14. (14) Herlev Hospital, grid.411900.d, Capital Region
  15. (15) Danish Cancer Society, grid.417390.8
  16. (16) Department of Obstetrics and Gynecology, The Juliane Marie Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Ø, Denmark
  17. (17) Department of Medical Oncology, Mayo Clinic, 200 First Street SW, Charlton 6, 55905, Rochester, MN, USA
  18. (18) University of Kansas Medical Center, grid.412016.0
  19. (19) Mayo Clinic, grid.66875.3a
  20. (20) Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Charlton 6, 55905, Rochester, MN, USA
  21. (21) Foothills Medical Centre, grid.414959.4
  22. (22) Addenbrooke's Hospital, grid.120073.7
  23. (23) NIHR Cambridge Dementia Biomedical Research Unit, grid.454369.9
  24. (24) Alberta Health Services, grid.413574.0
  25. (25) Royal Alexandra Hospital, grid.416087.c
  26. (26) Westmead Hospital, grid.413252.3
  27. (27) QIMR Berghofer Medical Research Institute, grid.1049.c
  28. (28) BC Cancer Agency, grid.248762.d
  29. (29) University of California, Los Angeles, grid.19006.3e
  30. (30) Cambridge Experimental Cancer Medicine Centre, CB2 0RE, Cambridge, UK
  31. (31) Cancer Research UK Cambridge Institute, grid.470869.4
  32. (32) Department of Public Health Sciences, Medical University of South Carolina and Hollings Cancer Center, 135 Cannon Street, 29425, Charleston, SC, USA

Description

BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1 expression. We conducted a large study evaluating FOLR1 expression with survival in different histological types of OvCa. METHODS: Tissue microarrays composed of tumour samples from 2801 patients in the Ovarian Tumour Tissue Analysis (OTTA) consortium were assessed for FOLR1 expression by centralised immunohistochemistry. We estimated associations for overall (OS) and progression-free (PFS) survival using adjusted Cox regression models. High-grade serous ovarian carcinomas (HGSC) from The Cancer Genome Atlas (TCGA) were evaluated independently for association between FOLR1 mRNA upregulation and survival. RESULTS: FOLR1 expression ranged from 76% in HGSC to 11% in mucinous carcinomas in OTTA. For HGSC, the association between FOLR1 expression and OS changed significantly during the years following diagnosis in OTTA (Pinteraction=0.01, N=1422) and TCGA (Pinteraction=0.01, N=485). In OTTA, particularly for FIGO stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259). In TCGA, FOLR1 mRNA upregulation in HGSC was also associated with increased OS during the first 2 years following diagnosis irrespective of tumour stage (HR: 0.48, 95% CI: 0.25-0.94). CONCLUSIONS: FOLR1-positive HGSC tumours were associated with an increased OS in the first 2 years following diagnosis. Patients with FOLR1-negative, poor prognosis HGSC would be unlikely to benefit from anti-FOLR1 therapies. In contrast, a decreased PFS interval was observed for FOLR1-positive CCC. The clinical efficacy of FOLR1-targeted interventions should therefore be evaluated according to histology, stage and time following diagnosis.

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University of Copenhagen

Danish Open Access Indicator

2014: Blocked

Research area: Medicine

Danish Bibliometrics Indicator

2014: Level 1

Research area: Medicine

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Times Cited: 34

Field Citation Ratio (FCR): 7.07

Relative Citation ratio (RCR): 1.64

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