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Article

FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases

  • Authors:
    • Gian Franco Zannoni
    • Giuseppina Improta
    • Marco Petrillo
    • Angela Pettinato
    • Giovanni Scambia
    • Filippo Fraggetta
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Catholic University of The Sacred Heart, I‑00168 Rome, Italy, Laboratory of Clinical Research and Advanced Diagnostics, Hospitalization and Treatment Institute Scientific‑Oncological Referral Center of Basilicata, I‑85028 Potenza, Italy, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, I‑00168 Rome, Italy, Department of Pathology, Cannizzaro Hospital, I-95126 Catania, Italy
  • Pages: 1159-1163
    |
    Published online on: June 14, 2016
       https://doi.org/10.3892/ol.2016.4711
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Abstract

Granulosa cell tumors (GCTs) of the ovary are uncommon neoplasms, accounting for ~5% of all malignant ovarian tumors. GCTs are a relatively homogeneous group of tumors, categorized into two distinct subtypes, juvenile GCT and adult GCT (AGCT), likely arising from a limited set of molecular events usually involving the disruption of pathways that regulate granulosa cell proliferation. In the present study, the presence of forkheadbox L2 (FOXL2) c.402C>G mutation was investigated in a series of 42 samples of primary and metastatic AGCT of the ovary. The samples consisted of 37 primary and 5 metastatic ovarian AGCTs from 37 patients. FOXL2 mutational status was evaluated using a pyrosequencing approach on 2.5‑µm sections of formalin‑fixed paraffin‑embedded tissue. FOXL2 c.402C>G mutation was found in 33/37 (89.2%) primary AGCTs and in 4/5 (80.0%) metastases, with the molecular status of the metastases recapitulating that of the primary tumors (4 mutated cases and 1 wild‑type case). Overall, FOXL2 mutation is present in the majority of primary and metastatic AGCTs, and could be used as a valid tool in the diagnosis of the disease and in cases of metastatic lesions from an unknown primary origin. Moreover the concordance of FOXL2 molecular status in primary and associated metastases suggests its early appearance and genomic stability in AGCT tumorigenesis.
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1 

Colombo N, Parma G, Zanagnolo V and Insinga A: Management of ovarian stromal cell tumors. J Clin Oncol. 25:2944–2951. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Young RH and Scully RE: Endocrine tumors of the ovary. Curr Top Pathol. 85:113–164. 1992. View Article : Google Scholar : PubMed/NCBI

3 

Fox H, Agrawal K and Langley FA: A clinicopathologic study of 92 cases of granulosa cell tumor of the ovary with special reference to the factors influencing prognosis. Cancer. 35:231–241. 1975. View Article : Google Scholar : PubMed/NCBI

4 

Fuller PJ, Chu S, Fikret S and Burger HG: Molecular pathogenesis of granulosa cell tumours. Mol Cell Endocrinol. 191:89–96. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Jamieson S and Fuller PJ: Management of granulosa cell tumour of the ovary. Curr Opin Oncol. 20:560–564. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Chu S, Rushdi S, Zumpe ET, Mamers P, Healy DL, Jobling T, Burger HG and Fuller PJ: FSH-regulated gene expression profiles in ovarian tumours and normal ovaries. Mol Hum Reprod. 8:426–433. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Fuller PJ and Chu S: Signaling pathways in the molecular pathogenesis of ovarian granulosa cell tumours. Trends Endocrinol Metab. 15:122–128. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Anttonen M, Unkila-Kallio L, Leminen A, Butzow R and Heikinheimo M: High GATA-4 expression associates with aggressive behavior, whereas low anti-Müllerian hormone expression associates with growth potential of ovarian granulosa cell tumors. J Clin Endocrinol Metab. 90:6529–6235. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Shah SP, Köbel M, Senz J, Morin RD, Clarke BA, Wiegand KC, Leung G, Zayed A, Mehl E, Kalloger SE, et al: Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med. 360:2719–2729. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Schrader KA, Gorbatcheva B, Senz J, Heravi-Moussavi A, Melnyk N, Salamanca C, Maines-Bandiera S, Cooke SL, Leung P, Brenton JD, et al: The specificity of the FOXL2 c.402C>G somatic mutation: A survey of solid tumors. PLoS One. 4:e79882009. View Article : Google Scholar : PubMed/NCBI

11 

Kim MS, Hur SY, Yoo NJ and Lee SH: Mutational analysis of FOXL2 codon 134 in granulosa cell tumour of ovary and other human cancers. J Pathol. 221:147–152. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Berek JS, Crum C and Friedlander M: Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 131(Suppl 2): S111–S122. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Zaloudek CJ, Mooney EE, Staats PN and Young RH: Tumours of the ovary and peritoneum. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Kurman R, Carcangiu ML, Herrington CS and Young RH: IARC Press; Lyon: pp. 1462014

14 

Rosario R, Wilson M, Cheng WT, Payne K, Cohen PA, Fong P and Shelling AN: Adult granulosa cell tumours (GCT): Clinicopathological outcomes including FOXL2 mutational status and expression. Gynecol Oncol. 131:325–329. 2013. View Article : Google Scholar : PubMed/NCBI

15 

D'Angelo E, Mozos A, Nakayama D, Espinosa I, Catasus L, Muñoz J and Prat J: Prognostic significance of FOXL2 mutation and mRNA expression in adult and juvenile granulosa cell tumors of the ovary. Mod Pathol. 24:1360–1367. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Kommoss S, Gilks CB, Penzel R, Herpel E, Mackenzie R, Huntsman D, Schirmacher P, Anglesio M, Schmidt D and Kommoss F: A current perspective on the pathological assessment of FOXL2 in adult-type granulosa cell tumours of the ovary. Histopathology. 64:380–388. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, et al: Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell. 139:1130–1142. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Cocquet J, De Baere E, Gareil M, Pannetier M, Xia X, Fellous M and Veitia RA: Structure, evolution and expression of the FOXL2 transcription unit. Cytogenet Genome Res. 101:206–211. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Cocquet J, Pailhoux E, Jaubert F, Servel N, Xia X, Pannetier M, De Baere E, Messiaen L, Cotinot C, Fellous M and Veitia RA: Evolution and expression of FOXL2. J Med Genet. 39:916–921. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, Bisceglia L, Zelante L, Nagaraja R, Porcu S, et al: The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet. 27:159–166. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Duffin K, Bayne RA, Childs AJ, Collins C and Anderson RA: The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formation. Mol Hum Reprod. 15:771–777. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Crisponi L, Uda M, Deiana M, Loi A, Nagaraja R, Chiappe F, Schlessinger D, Cao A and Pilia G: FOXL2 inactivation by a translocation 171 kb away: Analysis of 500 kb of chromosome 3 for candidate long-range regulatory sequences. Genomics. 83:757–764. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Beysen D, Vandesompele J, Messiaen L, De Paepe A and De Baere E: The human FOXL2 mutation database. Hum Mutat. 24:189–193. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Harris SE, Chand AL, Winship IM, Gersak K, Aittomäki K and Shelling AN: Identification of novel mutations in FOXL2 associated with premature ovarian failure. Mol Hum Reprod. 8:729–733. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Kim T, Sung CO, Song SY, Bae DS and Choi YL: FOXL2 mutation in granulosa-cell tumours of the ovary. Histopathology. 56:408–410. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Jamieson S, Butzow R, Andersson N, Alexiadis M, Unkila-Kallio L, Heikinheimo M, Fuller PJ and Anttonen M: The FOXL2 C134 W mutation is characteristic of adult granulosa cell tumors of the ovary. Mod Pathol. 23:1477–1485. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Al-Agha OM, Huwait HF, Chow C, Yang W, Senz J, Kalloger SE, Huntsman DG, Young RH and Gilks CB: FOXL2 is a sensitive and specific marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol. 35:484–494. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Benayoun BA, Caburet S, Dipietromaria A, Georges A, D'Haene B, Pandaranayaka PJ, L'Hôte D, Todeschini AL, Krishnaswamy S, Fellous M, et al: Functional exploration of the adult ovarian granulosa cell tumor-associated somatic FOXL2 mutation p.Cys134Trp (c.402C>G). PLoS One. 5:e87892010. View Article : Google Scholar : PubMed/NCBI

29 

Kommoss S, Anglesio MS, Mackenzie R, Yang W, Senz J, Ho J, Bell L, Lee S, Lorette J, Huntsman DG and Blake Gilks C: FOXL2 molecular testing in ovarian neoplasms: Diagnostic approach and procedural guidelines. Mod Pathol. 26:860–867. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Benayoun BA, Anttonen M, L'Hôte D, Bailly-Bechet M, Andersson N, Heikinheimo M and Veitia RA: Adult ovarian granulosa cell tumor transcriptomics: Prevalence of FOXL2 target genes misregulation gives insights into the pathogenic mechanism of the p.Cys134Trp somatic mutation. Oncogene. 32:2739–2746. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Rosario R, Araki H, Print CG and Shelling AN: The transcriptional targets of mutant FOXL2 in granulosa cell tumours. PLoS One. 7:e462702012. View Article : Google Scholar : PubMed/NCBI

32 

Soh J, Okumura N, Lockwood WW, Yamamoto H, Shigematsu H, Zhang W, Chari R, Shames DS, Tang X, MacAulay C, et al: Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells. PLoS One. 4:e74642009. View Article : Google Scholar : PubMed/NCBI

33 

Improta G, Pelosi G, Tamborini E, Donia M, Santinami M, de Braud F and Fraggetta F: Biological insights into BRAFV600 mutations in melanoma patient: Not mere therapeutic targets. Oncoimmunology. 2:e255942013. View Article : Google Scholar : PubMed/NCBI

34 

Geiersbach KB, Jarboe EA, Jahromi MS, Baker CL, Paxton CN, Tripp SR and Schiffman JD: FOXL2 mutation and large-scale genomic imbalances in adult granulosa cell tumors of the ovary. Cancer Genet. 204:596–602. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zannoni GF, Improta G, Petrillo M, Pettinato A, Scambia G and Fraggetta F: FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases. Oncol Lett 12: 1159-1163, 2016.
APA
Zannoni, G.F., Improta, G., Petrillo, M., Pettinato, A., Scambia, G., & Fraggetta, F. (2016). FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases. Oncology Letters, 12, 1159-1163. https://doi.org/10.3892/ol.2016.4711
MLA
Zannoni, G. F., Improta, G., Petrillo, M., Pettinato, A., Scambia, G., Fraggetta, F."FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases". Oncology Letters 12.2 (2016): 1159-1163.
Chicago
Zannoni, G. F., Improta, G., Petrillo, M., Pettinato, A., Scambia, G., Fraggetta, F."FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases". Oncology Letters 12, no. 2 (2016): 1159-1163. https://doi.org/10.3892/ol.2016.4711
Copy and paste a formatted citation
x
Spandidos Publications style
Zannoni GF, Improta G, Petrillo M, Pettinato A, Scambia G and Fraggetta F: FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases. Oncol Lett 12: 1159-1163, 2016.
APA
Zannoni, G.F., Improta, G., Petrillo, M., Pettinato, A., Scambia, G., & Fraggetta, F. (2016). FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases. Oncology Letters, 12, 1159-1163. https://doi.org/10.3892/ol.2016.4711
MLA
Zannoni, G. F., Improta, G., Petrillo, M., Pettinato, A., Scambia, G., Fraggetta, F."FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases". Oncology Letters 12.2 (2016): 1159-1163.
Chicago
Zannoni, G. F., Improta, G., Petrillo, M., Pettinato, A., Scambia, G., Fraggetta, F."FOXL2 molecular status in adult granulosa cell tumors of the ovary: A study of primary and metastatic cases". Oncology Letters 12, no. 2 (2016): 1159-1163. https://doi.org/10.3892/ol.2016.4711
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