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

被引：76

作者：

Koebel, M. ^{[1
]}

Madore, J. ^{[2
,3
]}

Ramus, S. J. ^{[4
]}

Clarke, B. A. ^{[5
]}

Pharoah, P. D. P. ^{[6
,7
]}

Deen, S. ^{[8
]}

Bowtell, D. D. ^{[9
,10
,11
]}

Odunsi, K. ^{[12
]}

Menon, U. ^{[13
]}

Morrison, C. ^{[14
]}

Lele, S.

Bshara, W. ^{[14
]}

Sucheston, L. ^{[15
]}

Beckmann, M. W. ^{[16
]}

Hein, A. ^{[16
]}

Thiel, F. C. ^{[16
]}

Hartmann, A. ^{[17
]}

Wachter, D. L. ^{[17
]}

Anglesio, M. S. ^{[2
]}

Hogdall, E. ^{[18
,19
]}

Jensen, A. ^{[18
]}

Hogdall, C. ^{[20
]}

Kalli, K. R. ^{[21
]}

Fridley, B. L. ^{[22
]}

Keeney, G. L. ^{[23
]}

Fogarty, Z. C. ^{[24
]}

Vierkant, R. A. ^{[24
]}

Liu, S. ^{[25
]}

Cho, S. ^{[1
]}

Nelson, G. ^{[26
]}

Ghatage, P. ^{[26
]}

Gentry-Maharaj, A. ^{[13
]}

Gayther, S. A. ^{[4
]}

Benjamin, E. ^{[27
]}

Widschwendter, M. ^{[28
]}

Intermaggio, M. P. ^{[4
]}

Rosen, B. ^{[29
]}

Bernardini, M. Q. ^{[29
]}

Mackay, H. ^{[30
]}

Oza, A. ^{[29
]}

Shaw, P. ^{[29
]}

Jimenez-Linan, M. ^{[31
,32
]}

Driver, K. E. ^{[7
]}

Alsop, J. ^{[7
]}

Mack, M. ^{[7
]}

Koziak, J. M. ^{[33
]}

Steed, H. ^{[34
]}

Ewanowich, C. ^{[35
]}

DeFazio, A. ^{[36
,37
]}

Chenevix-Trench, G. ^{[38
]}

机构：

[1] Univ Calgary, Dept Pathol & Lab Med, Foothills Med Ctr, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada

[2] Univ British Columbia, Dept Pathol & Lab Med, BC Cancer Agcy, 600 West 10th Ave, Vancouver, BC V5E 4E6, Canada

[3] Univ Sydney, Royal Prince Alfred Hosp, Melanoma Inst Australia, Gloucester House level 3,Missenden Rd, Camperdown, NSW 2050, Australia

[4] Univ Southern Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med,USC,Off 2517G, Harlyne Norris Res Tower, 1450 Biggy St, Los Angeles, CA 90033 USA

[5] Univ Toronto, Princess Margaret Canc Ctr, Dept Lab Med & Pathobiol, 610 Univ Ave,M-700, Toronto, ON M5T 2M9, Canada

[6] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England

[7] Univ Cambridge, Dept Oncol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England

[8] Nottingham Univ Hosp NHS Trust, Dept Histopathol, Queens Med Ctr, Nottingham NG7 2UH, England

[9] Peter MacCallum Canc Ctr, Dept Canc Genom & Genet, Locked Bag I,A Beckett St, East Melbourne, Vic 8006, Australia

[10] Univ Melbourne, Dept Biochem & Mol Biol, 30 Flemington Rd, Melbourne, Vic 3010, Australia

[11] Univ Melbourne, Sir Peter MacCallum Dept Oncol, 30 Flemington Rd, Melbourne, Vic 3010, Australia

[12] Roswell Pk Canc Inst, Dept Gynecol Oncol, Elm & Carlton St, Buffalo, NY 14263 USA

[13] UCL, Inst Womens Hlth, Dept Womens Canc, Gynaecol Canc Res Ctr, Maple House 1st Floor,149 Tottenham Court Rd, London W1T 7DN, England

[14] Roswell Pk Canc Inst, Dept Pathol & Lab Med, Elm & Carlton St, Buffalo, NY 14263 USA

[15] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Elm & Carlton St, Buffalo, NY 14263 USA

[16] Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Univ Str 21-23, D-91054 Erlangen, Germany

[17] Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Inst Pathol, Krankenhausstr 8-10, D-91054 Erlangen, Germany

[18] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Strandboule Varden 49, DK-2100 Copenhagen O, Denmark

[19] Univ Copenhagen, Herlev Hosp, Dept Pathol, Herlev Ringvej 75, DK-2370 Herlev, Denmark

[20] Univ Copenhagen, Rigshosp, Dept Obstet & Gynecol, Juliane Marie Ctr, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark

[21] Mayo Clin, Dept Med Oncol, 200 First Street SW,Charlton 6, Rochester, MN 55905 USA

[22] Univ Kansas, Med Ctr, Dept Biostat, 3901 Rainbow Blvd, Kansas City, KS 66160 USA

[23] Mayo Clin, Div Anat Pathol, Dept Lab Med & Pathol, 200 First St SW,Stabile 13, Rochester, MN 55905 USA

[24] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, 200 First St SW,Charlton 6, Rochester, MN 55905 USA

[25] Foothills Med Ctr, Calgary Lab Serv, Anat Pathol Res Lab, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada

[26] Univ Calgary, Foothills Med Ctr, Tom Baker Canc Ctr, Dept Obstet & Gynecol,Div Oncol, 1403 29 ST NW, Calgary, AB T2N 2T9, Canada

[27] UCL, Inst Canc, Dept Pathol, Maple House,149 Tottenham Court Rd, London WC1E 6JJ, England

[28] UCL, UCL EGA Inst Womens Hlth, Dept Womens Canc, 74 Huntley St, London WC1E 6AU, England

[29] Univ Toronto, Princess Margaret Canc Ctr, Dept Obstet & Gynecol, 610 Univy Ave,M-700, Toronto, ON M5T 2M9, Canada

[30] Univ Toronto, Princess Margaret Hosp, Div Med Oncol, Dept Med, 610 Univ Ave, Toronto, ON M5T 2M9, Canada

[31] Univ Cambridge Hosp NHS Fdn Trust, Dept Pathol, Addenbrookes Hosp, Hills Rd, Cambridge CB2 0QQ, England

[32] Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge CB2 2QQ, England

[33] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, 2210 2nd St SW, Calgary, AB T2S 3C3, Canada

[34] Royal Alexandra Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, 10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada

[35] Royal Alexandra Hosp, Dept Lab Med & Pathol, 10240 Kingsway Ave, Edmonton, AB T5H 3V9, Canada

[36] Univ Sydney, Westmead Millennium Inst, Dept Gynaecol Oncol, Westmead Hosp, Westmead, NSW 2145, Australia

[37] Univ Sydney, Westmead Inst Canc Res, Westmead Millennium Inst, Westmead Hosp, Westmead, NSW 2145, Australia

[38] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, 300 Herston Rd, Herston, Qld 4006, Australia

[39] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, 200 First St SW Charlton 6, Rochester, MN 55905 USA

[40] British Columbia Canc Agcy, Ctr Translat & Appl Gen, 600 West 10th Ave, Vancouver, BC V5Z 4E6, Canada

[41] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA

[42] Univ Cambridge, Hutchison MRC Res Ctr, Dept Oncol, Hills Rd, Cambridge CB2 0XZ, England

[43] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England

[44] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England

[45] Med Univ South Carolina, Dept Publ Hlth Sci, 135 Cannon St, Charleston, SC 29425 USA

[46] Hollings Canc Ctr, 135 Cannon St, Charleston, SC 29425 USA

来源：

BRITISH JOURNAL OF CANCER | 2014年 / 111卷 / 12期

关键词：

ovarian cancer; folate receptor alpha; FRA; immunohistochemistry; prognosis; TCGA; FOLATE-RECEPTOR-ALPHA; EPITHELIAL OVARIAN; MONOCLONAL-ANTIBODY; CANCER; RISK; FARLETUZUMAB; BINDING; PROGNOSIS; THERAPY; WOMEN;

D O I：

10.1038/bjc.2014.567

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (P-interaction = 0.01, N = 1422) and TCGA (P-interaction = 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.

引用

页码：2297 / 2307

页数：11

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