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

Koebel M, Madore J, Ramus SJ, Clarke BA, Pharoah PDP, Deen S, Bowtell DD, Odunsi K, Menon U, Morrison C, Lele S, Bshara W, Sucheston L, Beckmann M, Hein A, Thiel F, Hartmann A, Wachter D, Anglesio MS, Hogdall E, Jensen A, Hogdall C, Kalli KR, Fridley BL, Keeney GL, Fogarty ZC, Vierkant RA, Liu S, Cho S, Nelson G, Ghatage P, Gentry-Maharaj A, Gayther SA, Benjamin E, Widschwendter M, Intermaggio MP, Rosen B, Bernardini MQ, Mackay H, Oza A, Shaw P, Jimenez-Linan M, Driver KE, Alsop J, Mack M, Koziak JM, Steed H, Ewanowich C, Defazio A, Chenevix-Trench G, Fereday S, Gao B, Johnatty SE, George J, Galletta L, Goode EL, Kjaer SK, Huntsman DG, Fasching P, Moysich KB, Brenton JD, Kelemen LE (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 111

Pages Range: 2297-307

Journal Issue: 12

DOI: 10.1038/bjc.2014.567

Abstract

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.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.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).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.

Authors with CRIS profile

Involved external institutions

Danish Cancer Society Research Center Denmark (DK) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Medical University of South Carolina (MUSC) United States (USA) (US) University of Cambridge United Kingdom (GB) British Columbia Cancer Agency Canada (CA) University of Copenhagen Denmark (DK) Mayo Clinic United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) University of Sydney (USYD) Australia (AU) Royal Alexandra Hospital (RAH) Canada (CA) Alberta Health Services (AHS) Canada (CA) University of Toronto Canada (CA) University of Southern California (USC) United States (USA) (US) University College London (UCL) United Kingdom (GB) University of Calgary Canada (CA) Foothills Medical Centre (FMC) Canada (CA) University of Kansas (KU) United States (USA) (US) University of British Columbia Canada (CA) Roswell Park Cancer Institute United States (USA) (US) University of Nottingham United Kingdom (GB)

How to cite

APA:

Koebel, M., Madore, J., Ramus, S.J., Clarke, B.A., Pharoah, P.D.P., Deen, S.,... Kelemen, L.E. (2014). 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, 111(12), 2297-307. https://dx.doi.org/10.1038/bjc.2014.567

MLA:

Koebel, M., et al. "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 111.12 (2014): 2297-307.

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