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
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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. / Köbel, M; Madore, J; Ramus, S J; Clarke, B A; Pharoah, P D P; Deen, S; Bowtell, D D; Odunsi, K; Menon, U; Morrison, C; Lele, S; Bshara, W; Sucheston, L; Beckmann, M W; Hein, A; Thiel, F C; Hartmann, A; Wachter, D L; Anglesio, M S; Høgdall, E; Jensen, A; Høgdall, C; Kalli, K R; Fridley, B L; Keeney, G L; Fogarty, Z C; Vierkant, R A; Liu, S; Cho, S; Nelson, G; Ghatage, P; Gentry-Maharaj, A; Gayther, S A; Benjamin, E; Widschwendter, M; Intermaggio, M P; Rosen, B; Bernardini, M Q; Mackay, H; Oza, A; Shaw, P; Jimenez-Linan, M; Driver, K E; Alsop, J; Mack, M; Koziak, J M; Steed, H; Ewanowich, C; DeFazio, A; Kjær, S K; AOCS Study Group.
I: B J C, Bind 111, Nr. 12, 12.2014, s. 2297–2307.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma
T2 - implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study
AU - Köbel, M
AU - Madore, J
AU - Ramus, S J
AU - Clarke, B A
AU - Pharoah, P D P
AU - Deen, S
AU - Bowtell, D D
AU - Odunsi, K
AU - Menon, U
AU - Morrison, C
AU - Lele, S
AU - Bshara, W
AU - Sucheston, L
AU - Beckmann, M W
AU - Hein, A
AU - Thiel, F C
AU - Hartmann, A
AU - Wachter, D L
AU - Anglesio, M S
AU - Høgdall, E
AU - Jensen, A
AU - Høgdall, C
AU - Kalli, K R
AU - Fridley, B L
AU - Keeney, G L
AU - Fogarty, Z C
AU - Vierkant, R A
AU - Liu, S
AU - Cho, S
AU - Nelson, G
AU - Ghatage, P
AU - Gentry-Maharaj, A
AU - Gayther, S A
AU - Benjamin, E
AU - Widschwendter, M
AU - Intermaggio, M P
AU - Rosen, B
AU - Bernardini, M Q
AU - Mackay, H
AU - Oza, A
AU - Shaw, P
AU - Jimenez-Linan, M
AU - Driver, K E
AU - Alsop, J
AU - Mack, M
AU - Koziak, J M
AU - Steed, H
AU - Ewanowich, C
AU - DeFazio, A
AU - Kjær, S K
AU - AOCS Study Group
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
KW - Disease-Free Survival
KW - Female
KW - Folate Receptor 1
KW - Humans
KW - Immunohistochemistry
KW - Middle Aged
KW - Neoplasms, Glandular and Epithelial
KW - Ovarian Neoplasms
KW - Survival Analysis
KW - Tissue Array Analysis
KW - Tumor Markers, Biological
U2 - 10.1038/bjc.2014.567
DO - 10.1038/bjc.2014.567
M3 - Journal article
C2 - 25349970
VL - 111
SP - 2297
EP - 2307
JO - The British journal of cancer. Supplement
JF - The British journal of cancer. Supplement
SN - 0007-0920
IS - 12
ER -
ID: 137511319