Evidence map›Paper›PMID 25349970›Full record

ArticleBritish journal of cancer2014

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.

M Köbel, J Madore, S J Ramus, B A Clarke, P D P Pharoah, S Deen, D D Bowtell, K Odunsi, U Menon, C Morrison and 53 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
7.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 103 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Folate receptor alpha in platinum-resistant ovarian cancer: prevalence in a multicenter Polish cohort and review of the evidence.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment?International journal of molecular sciences · 2024
    Review
  17. Review
  18. Article
  19. Review
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

63 authors at 20 institutions in 7 countries.

M KöbelDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada.
J Madore1] Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5E 4E6, Canada [2] Melanoma Institute Australia, University of Sydney, Royal Prince Alfred Hospital, Gloucester House-level 3, Missenden Road, Camperdown, NSW 2050, Australia.
S J RamusDepartment of Preventive Medicine, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, Harlyne Norris Research Tower, 1450 Biggy Street, Office 2517G, Los Angeles, CA 90033, USA.
B A ClarkeDepartment of Laboratory Medicine and Pathobiology, Princess Margaret Cancer Centre, University of Toronto, 610 Univeristy Avenue, M-700, Toronto, ON M5T 2M9, Canada.
P D P Pharoah1] Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK [2] Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
S DeenDepartment of Histopathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK.
D D Bowtell1] Department of Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Locked Bag I, A'Beckett Street, East Melbourne, VIC 8006, Australia [2] Department of Biochemistry and Molecular Biology, University of Melbourne, 30 Flemington Road, Melbourne, VIC 3010, Australia [3] Sir Peter MacCallum Department of Oncology, University of Melbourne, 30 Flemington Road, Melbourne, VIC 3010, Australia.
K OdunsiDepartment of Gynecological Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
U MenonGynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, University College London, Maple House 1st Floor, 149 Tottenham Court Road, London W1T 7DN, UK.
C MorrisonDepartment of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
S Lele1] Department of Gynecological Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA [2] Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
W BsharaDepartment of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
L SuchestonDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
M W BeckmannDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
A HeinDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
F C ThielDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany.
A HartmannInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Krankenhausstrasse 8-10, 91054 Erlangen, Germany.
D L WachterInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Krankenhausstrasse 8-10, 91054 Erlangen, Germany.
M S AnglesioDepartment of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5E 4E6, Canada.
E Høgdall1] Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Ø, Denmark [2] Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, DK-2370 Herlev, Denmark.
A JensenDepartment of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Ø, Denmark.
C HøgdallThe Juliane Marie Center, Department of Obstetrics and Gynecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Ø, Denmark.
K R KalliDepartment of Medical Oncology, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN 55905, USA.
B L FridleyDepartment of Biostatistics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
G L KeeneyDepartment of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Stabile 13, Rochester, MN 55905, USA.
Z C FogartyDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN 55905, USA.
R A VierkantDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Charlton 6, Rochester, MN 55905, USA.
S LiuAnatomic Pathology Research Laboratory, Calgary Laboratory Services, Foothills Medical Center, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada.
S ChoDepartment of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada.
G NelsonDepartment of Obstetrics and Gynecology, Division of Oncology, Tom Baker Cancer Centre, University of Calgary, Foothills Medical Center, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada.
P GhatageDepartment of Obstetrics and Gynecology, Division of Oncology, Tom Baker Cancer Centre, University of Calgary, Foothills Medical Center, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada.
A Gentry-MaharajGynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, University College London, Maple House 1st Floor, 149 Tottenham Court Road, London W1T 7DN, UK.
S A GaytherDepartment of Preventive Medicine, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, Harlyne Norris Research Tower, 1450 Biggy Street, Office 2517G, Los Angeles, CA 90033, USA.
E BenjaminDepartment of Pathology, Cancer Institute, University College London, Maple House, 149 Tottenham Court Road, London WC1E 6JJ, UK.
M WidschwendterDepartment of Women's Cancer, UCL EGA Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, UK.
M P IntermaggioDepartment of Preventive Medicine, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, Harlyne Norris Research Tower, 1450 Biggy Street, Office 2517G, Los Angeles, CA 90033, USA.
B RosenDepartment of Obstetrics and Gynecology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, M-700, Toronto, ON M5T 2M9, Canada.
M Q BernardiniDepartment of Obstetrics and Gynecology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, M-700, Toronto, ON M5T 2M9, Canada.
H MackayDepartment of Medicine, Division of Medical Oncology, University of Toronto, Princess Margaret Hospital, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
A OzaDepartment of Obstetrics and Gynecology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, M-700, Toronto, ON M5T 2M9, Canada.
P ShawDepartment of Obstetrics and Gynecology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, M-700, Toronto, ON M5T 2M9, Canada.
M Jimenez-Linan1] Department of Pathology, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK [2] National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge CB2 2QQ, UK.
K E DriverDepartment of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
J AlsopDepartment of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
M MackDepartment of Oncology, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
J M KoziakDepartment of Population Health Research, Alberta Health Services-Cancer Care, 2210 2nd Street SW, Calgary, AB, T2S 3C3, Canada.
H SteedDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, 10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada.
C EwanowichDepartment of Laboratory Medicine and Pathology, Royal Alexandra Hospital, 10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada.
A DeFazioDepartment of Gynaecological Oncology and Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia.
G Chenevix-TrenchGenetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD,4006, Australia.
S FeredayDepartment of Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Locked Bag I, A'Beckett Street, East Melbourne, VIC 8006, Australia.
B GaoDepartment of Gynaecological Oncology and Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia.
S E JohnattyGenetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD,4006, Australia.
J GeorgeDepartment of Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Locked Bag I, A'Beckett Street, East Melbourne, VIC 8006, Australia.
L GallettaDepartment of Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Locked Bag I, A'Beckett Street, East Melbourne, VIC 8006, Australia.
AOCS Study Group
E L GoodeDepartment of Health Sciences Research, Division of Epidemiology, Mayo Clinic, 200 First Street SW Charlton 6, Rochester, MN 55905, USA.
S K Kjær1] Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Ø, Denmark [2] The Juliane Marie Center, Department of Obstetrics and Gynecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Ø, Denmark.
D G Huntsman1] Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5E 4E6, Canada [2] Centre For Translational and Applied Genomics, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
P A Fasching1] Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitaetsstrasse 21-23, 91054 Erlangen, Germany [2] Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
K B MoysichDepartment of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
J D Brenton1] National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge CB2 2QQ, UK [2] Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Hills Road, Cambridge CB2 0XZ, UK [3] Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [4] Cambridge Experimental Cancer Medicine Centre, Cambridge CB2 0RE, UK.
L E KelemenDepartment of Public Health Sciences, Medical University of South Carolina and Hollings Cancer Center, 135 Cannon Street, Charleston, SC 29425, USA.
Roswell Park Comprehensive Cancer Center · USMayo Clinic · USUniversity of Southern California · USUniversity of Toronto · CABC Cancer Agency · CAQIMR Berghofer Medical Research Institute · AUUniversitätsklinikum Erlangen · DEUniversity of Calgary · CAUniversity of Copenhagen · DKUniversity of Cambridge · GBAlberta Health Services · CANottingham University Hospitals NHS Trust · GBThe University of Sydney · AUBreast Cancer Now · GBCambridge University Hospitals NHS Foundation Trust · GBHerlev Hospital · DKInstitute of Cancer Research · GBMedical University of South Carolina · USMUSC Hollings Cancer Center · USPeter MacCallum Cancer Centre · AU

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI Zhenkun Lou · 2009 to 2026
$37.0M
RPCI-UPCI Ovarian Cancer SPOREP50CA159981 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B. · 2013 to 2025
$19.6M
Regulatory T Cell Function in Ovarian CancerR01CA126841 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MOYSICH, KIRSTEN B. · 2009 to 2013
$3.0M
Genetic Variation in the NF-kappaB Pathway and Ovarian Cancer EtiologyR01CA122443 · NCI · MAYO CLINIC ROCHESTER · PI GOODE, ELLEN L. · 2007 to 2012
$2.7M
RISK FACTORS AND PROGNOSTIC FACTORS FOR OVARIAN CANCERR01CA061107 · NCI · DANISH CANCER SOCIETY · PI KJAER, SUSANNE K · 1993 to 1995
–
Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 15601Cancer Research UK 16561Cancer Research UK C490/A10119Cancer Research UK C490/A10124CIHR MOP-86727CIHR MSH-87734NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA136393NCI NIH HHS P50CA136393NCI NIH HHS P50 CA159981NCI NIH HHS R01 CA122443NCI NIH HHS R01CA122443NCI NIH HHS R01 CA126841NCI NIH HHS R01CA61107
6 · The paper itself

Abstract

backgroundFolate 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.

methodsTissue 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.

resultsFOLR1 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).

conclusionsFOLR1-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.

Indexed as

Biomarkers, TumorCarcinoma, Ovarian EpithelialDisease-Free SurvivalFemaleFolate Receptor 1HumansImmunohistochemistryMiddle AgedNeoplasms, Glandular and EpithelialOvarian NeoplasmsSurvival AnalysisTissue Array AnalysisBiomarkers, TumorFolate Receptor 1FOLR1 protein, human

Identifiers

PMID25349970
PMCPMC4264456
OpenAlexW2080370558

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.